The DOI matches its Crossref record; 97 of the 97 references it cites were found in a registry or an index; 19 of the 47 sources its claims cite were checked for support.
Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes
Open accessAbstract
We have conducted a comprehensive search for conserved elements in vertebrate genomes, using genome-wide multiple alignments of five vertebrate species (human, mouse, rat, chicken, and Fugu rubripes ). Parallel searches have been performed with multiple alignments of four insect species (three species of Drosophila and Anopheles gambiae ), two species of Caenorhabditis , and seven species of Saccharomyces . Conserved elements were identified with a computer program called phastCons, which is based on a two-state phylogenetic hidden Markov model (phylo-HMM). PhastCons works by fitting a phylo-HMM to the data by maximum likelihood, subject to constraints designed to calibrate the model across species groups, and then predicting conserved elements based on this model. The predicted elements cover roughly 3%–8% of the human genome (depending on the details of the calibration procedure) and substantially higher fractions of the more compact Drosophila melanogaster (37%–53%), Caenorhabditis elegans (18%–37%), and Saccharaomyces cerevisiae (47%–68%) genomes. From yeasts to vertebrates, in order of increasing genome size and general biological complexity, increasing fractions of conserved bases are found to lie outside of the exons of known protein-coding genes. In all groups, the most highly conserved elements (HCEs), by log-odds score, are hundreds or thousands of bases long. These elements share certain properties with ultraconserved elements, but they tend to be longer and less perfectly conserved, and they overlap genes of somewhat different functional categories. In vertebrates, HCEs are associated with the 3′ UTRs of regulatory genes, stable gene deserts, and megabase-sized regions rich in moderately conserved noncoding sequences. Noncoding HCEs also show strong statistical evidence of an enrichment for RNA secondary structure.
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Claims the paper makes
19 of 47 cited sources checked · 15 supported · 0 flagged · accuracy not yet measured
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Analyses of human and rodent genomes (Mouse Genome Sequencing Consortium 2002;Chiaromonte et al. 2003;Roskin et al. 2003;Cooper et al. 2004;Rat Genome Sequencing Project Consortium 2004) indicate that about 5% or more of bases in mammalian genomes are under purifying selection”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Abstract
What the sources say
- Not matchedcites Mouse Genome Sequencing Consortium 2002
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not checked — no full text of the sourcecites Chiaromonte et al. 2003 source
- Partly supportedcites Cooper et al. 2004 sourceExperimental — accuracy not yet measured
The Global Identification of Constrained Elements section estimates that 5.2% of the human genome evolves at 40% or less of the neutral rate and explains that slowly evolving functional sequences tend to be under purifying selection. The analysis compares human, mouse, and rat genomes, but the quantified estimate is for the human genome, not mammalian genomes generally. Page numbers are unavailable in our copy. (LLM, conf=0.82)
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The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Note that the vertebrate coverage is similar to recent estimates of 5%-8% for the share of the human genome that is under purifying selection”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Abstract
What the sources say
- Not checked — no full text of the sourcecites Chiaromonte et al. 2003 source
- Not checked — no full text of the sourcecites Roskin et al. 2003 source
- Supportedcites Cooper et al. 2004 source
In “Global Identification of Constrained Elements” (page not supplied), the paper estimates that 5.2% of the human genome evolves at 40% or less of the neutral rate and that 8% evolves at 50% or less. It cautions that the 8% figure is likely an overestimate, while describing the lower figure as more realistic. These are estimates of genomic constraint consistent with the cited 5%–8% range. (LLM, conf=0.91)
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In the paper
“The estimated “nonconserved” branch lengths for vertebrates were fairly consistent with recent results based on (apparently) neutrally evolving DNA in mammals (Cooper et al. 2004), but were not accurate representations of the neutral substitution process in all respects.”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Abstract
What the sources say
- Supportedcites Cooper et al. 2004 source
The citation identifies the mammalian neutral-rate estimates used for comparison; the assessment that the citing authors’ vertebrate estimates were fairly consistent is their own. In “Rates of Neutral Point Substitution” (page unavailable), Cooper et al. estimate branch lengths for human, mouse, and rat and a total neutral rate of 0.65 substitutions per site. (LLM, conf=0.90)
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The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Human genes with predicted miRNA targets appear to be somewhat enriched for 3Ј-UTR HCEs; examples include the genes for the eukaryotic translation initiation factor EIF4E, the methyl CpG-binding protein MECP, the DNA-binding proteins (and oncoproteins) MYC and MYCN, the homeobox protein NBPHOX, and the ubiquitin protein ligase UBE3A, which is mutated in Angelman syndrome (John et al. 2004).”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > HCEs in the 3Ј UTRs of vertebrate genes
What the sources say
- Partly supportedcites John et al. 2004 sourceExperimental — accuracy not yet measured
The Results (Overview of Mammalian miRNA Target Genes; page unavailable) report predicted human miRNA targets with conserved sites in their 3′ UTRs, and the Results (Components of RNPs Regulated by miRNAs; page unavailable) name c-myc as a predicted target. Our copy does not report enrichment of predicted target genes for 3′-UTR HCEs or substantiate the full list of examples in the claim. (LLM, conf=0.81)
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The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“It is likely that many conserved 3Ј-UTR sequences are involved in posttranscriptional regulatory mechanisms, e.g., by influencing subcellular localization, transcript stability, or translatability (Duret et al. 1993;Grzybowska et al. 2001;Mignone et al. 2002).”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > HCEs in the 3Ј UTRs of vertebrate genes
What the sources say
- Supportedcites Duret et al. 1993 source
In “Role of 3'-HCRs in post-transcriptional mechanisms of regulation” (page not supplied), the authors say conserved 3'-UTR regions are probably involved in post-transcriptional regulation. The section discusses their potential roles in mRNA localisation, stability and translation, matching the citing sentence’s qualified claim. (LLM, conf=0.92)
- Not checked — no full text of the sourcecites Grzybowska et al. 2001 source
- Not matchedcites Mignone et al. 2002
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“We also found several examples of D. melanogaster genes with predicted miRNA target sites and HCEs in their 3Ј UTRs, such as the Hox cluster genes Abd-B, Antp, Scr, and Ubx (Enright et al. 2003).”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > HCEs in the 3Ј UTRs of vertebrate genes
What the sources say
- Partly supportedcites Enright et al. 2003 sourceExperimental — accuracy not yet measured
The Results section ('Hox genes and body axis specification'; page unavailable) predicts miRNA targeting of Hox genes, explicitly including Scr and Abd-B, and says all three Bithorax-complex genes are likely targets. The paper also requires conservation of predicted target sites, but the passages do not establish that the named genes have HCEs in their 3′ UTRs; conservation under its prediction criteria is not the same as identifying HCEs. (LLM, conf=0.85)
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Every source the paper cites for this claim was checked and supports it.
In the paper
“while in insects, our estimates of these fractions for intronic and intergenic regions are roughly 1-1/2-2 ן higher than estimates based on D. melanogaster/D.virilis comparisons (Bergman and Kreitman 2001).”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Abstract
What the sources say
- Supportedcites Bergman and Kreitman 2001 source
The Results (Table 2; page not provided) report conserved fractions for both intergenic and intronic DNA from D. melanogaster/D. virilis comparisons. The cited paper supplies the baseline estimates; the 1.5–2-fold comparison is the citing authors’ comparison with their own estimates, not a result attributed to Bergman and Kreitman. (LLM, conf=0.90)
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The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Only a few of the 40 known sense/antisense pairs reviewed by Shendure and Church (2002) contain HCEs coinciding with regions of sense/antisense overlap.”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > HCEs in the 3Ј UTRs of vertebrate genes
What the sources say
- Partly supportedcites Shendure and Church 2002 sourceExperimental — accuracy not yet measured
The Background (page not provided) says Shendure and Church reviewed 40 known sense–antisense cases. The Discussion (page not provided) describes conservation coinciding with overlap in several candidate pairs, but does not establish that only a few of the 40 reviewed pairs contain HCEs at their overlap regions. (LLM, conf=0.87)
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Every source the paper cites for this claim was checked and supports it.
In the paper
“John et al. (2004) found a substantial enrichment for predicted miRNA targets among the genes for the fragile X mental retardation protein FMR1, the ELAV-like proteins, and the polyadenylation-binding proteins (CPEBs), and among the genes whose mRNAs are known to be bound by these proteins, suggesting that miRNAs play a critical role in the regulatory networks in which these genes participate.”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > HCEs in the 3Ј UTRs of vertebrate genes
What the sources say
- Supportedcites John et al. 2004 source
Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“To our knowledge, this is the first genome-wide survey and comparison of conserved elements in different groups of eukaryotic species (excluding comparisons primarily of proteomes; e.g., Rubin et al. 2000).”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Discussion
What the sources say
- Supportedcites Rubin et al. 2000 source
Rubin et al. is cited as an example of an earlier comparison primarily of proteomes, not as evidence that the citing authors' survey was the first. The Abstract and “Core Proteome” section describe comparisons of predicted proteins, protein families, and protein domains across eukaryotic genomes. (LLM, conf=0.93)
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- It may state two separate claims as one. 81
- Probably not a substantial claim. 28
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“The apparent connection with RNA editing occurs also in insects; the RNA-edited potassium channel genes shaker, ether-a-go-go, and slowpoke (Hoopengardner et al. 2003) each overlap four or more HCEs (see related observations by Glazov et al. 2005).”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Functional enrichment of genes associated with HCEs
What the sources say
- Not checked — no full text of the sourcecites Hoopengardner et al. 2003 source
- Supportedcites Glazov et al. 2005 source
Glazov et al. is cited for related observations, not explicitly for the count of four or more HCEs per gene. In ‘Identification of ultraconserved sequences in insects’ (page unavailable), the paper reports an association between long insect ultraconserved elements and ion-channel genes, six of which undergo extensive RNA editing; Table 3 lists Shaker, ether-a-go-go, and slowpoke among those genes. (LLM, conf=0.90)
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
Every source the paper cites for this claim was checked and supports it.
In the paper
“These findings are consistent with earlier reports of widespread conservation in 3Ј UTRs (Duret et al. 1993;Lipman 1997), some of which have noted an enrichment for genes for DNA-binding proteins (Duret et al. 1993).”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > HCEs in the 3Ј UTRs of vertebrate genes
What the sources say
- Supportedcites Duret et al. 1993 source
The Abstract reports highly conserved regions in vertebrate non-coding sequences and says functional constraints are generally stronger in 3′ non-coding regions. The section “3′-HCRs are preferentially found in genes that are essential to cell life” reports that these regions occur especially often in genes encoding DNA-binding proteins or cytoskeletal proteins. The supplied passages do not give page numbers. (LLM, conf=0.92)
- Supportedcites Lipman 1997 source
The opening passage in our copy (labelled ABSTRACT) reports that Duret et al. estimated conserved 3′ UTR regions in more than 30% of vertebrate mRNAs, and Lipman also describes conserved UTR blocks in a substantial fraction of vertebrate mRNAs. The citing sentence attributes the DNA-binding-protein enrichment specifically to Duret et al., not to Lipman, so that portion is outside this citation's scope. (LLM, conf=0.92)
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Margulies et al. (2003), using two different methods, found that 72% of bases in predicted conserved elements in the CFTR region were not in exons.Cooper et al. (2004) reported similar results based on wholegenome human/mouse/rat alignments.”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Abstract
What the sources say
- Not matchedcites Margulies et al. 2003
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Supportedcites Cooper et al. 2004 source
In “Global Identification of Constrained Elements” (page not supplied), Cooper et al. report that nonexonic conserved segments substantially outnumber exon-overlapping segments at every threshold, including 167,892 versus 43,031 at the strongest constraint threshold. The paper bases this analysis on whole-genome human, mouse, and rat alignments. This supports the attributed claim of similar results, without attributing Margulies et al.’s 72% figure to Cooper et al. (LLM, conf=0.92)
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- Not matched
Every source the paper cites for this claim was checked and supports it.
In the paper
“In worms, our estimates of the fractions of coding regions, introns, and intergenic regions that are conserved are fairly similar to estimates based on an early comparative study of C. elegans and C. briggsae (Shabalina and Kondrashov 1999)”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Abstract
What the sources say
- Supportedcites Shabalina and Kondrashov 1999 source
The Results report estimated selective constraint of about 72% in exons, 17% in introns, and 18% in intergenic sequences for the C. elegans/C. briggsae comparison. The Discussion likewise presents these as conservative estimates. The citing authors’ assessment that their own estimates are fairly similar is not a finding attributed to this source. (LLM, conf=0.92)
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“These numbers are in good agreement both with bulk statistical estimates, based on genome-wide human/mouse and human/ mouse/rat alignments, of the share of the human genome that is under selection (Chiaromonte et al. 2003;Roskin et al. 2003;Cooper et al. 2004), and with an analysis of conserved elements in the region of the CFTR gene (Margulies et al. 2003;Thomas et al. 2003).”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Abstract
What the sources say
- Not checked — no full text of the sourcecites Chiaromonte et al. 2003 source
- Not checked — no full text of the sourcecites Roskin et al. 2003 source
- Supportedcites Cooper et al. 2004 source
The Global Identification of Constrained Elements section estimates that about 5.2% of the human genome evolves at 40% or less of the neutral rate and says this agrees with estimates from human–mouse and human–mouse–rat comparisons. Cooper et al. is cited for that genome-wide estimate; the citing sentence attributes the separate CFTR-region comparison to Margulies et al. and Thomas et al. (LLM, conf=0.92)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
Every source the paper cites for this claim was checked and supports it.
In the paper
“This program shows good accuracy in simulation experiments (Blanchette et al. 2004), and our synteny filters help to ensure that only orthologous conserved elements are considered, but whole-genome alignment is a difficult problem, and programs that address it are still in their infancy.”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Discussion
What the sources say
- Supportedcites Blanchette et al. 2004 source
The Evaluation of Alignment Accuracy section reports that MULTIZ achieved simulated human–mouse alignment accuracy almost as good as TBA’s; it also reports relatively high sensitivity and specificity. The citation attaches to MULTIZ’s simulated accuracy. The synteny filters are described as the citing authors’ own, not attributed to Blanchette et al. (LLM, conf=0.91)
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- Supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The remaining predicted elements cover 4.3% of the human genome, 44.5% of D. melanogaster, 26.4% of C. elegans, and 55.6% of S. cerevisiae.”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Abstract
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In the paper
“Various different methods produced coverage estimates of 2.8%-8.1% for the vertebrates, 36.9%-53.1% for the insects, 18.4%-36.6%for the worms, and 46.5%-67.6%for the yeasts (see Supplemental material).”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Abstract
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In the paper
“This trend is less pronounced in insects and was not observed in worms.”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Abstract
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In the paper
“Introns of known genes and unannotated (putative intergenic) regions contain significant fractions of conserved bases (3.6% coverage for introns and 2.7% coverage for unannotated regions), but smaller fractions than would be expected by chance.”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Abstract
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The 1.18 million vertebrate elements, in addition to covering 66% of the bases in known coding regions (approximately the target level), cover 23% of the bases in known 5Ј UTRs and 18% of the bases in known 3Ј UTRs”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Abstract
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In the paper
“The predicted elements cover roughly 3%-8% of the human genome (depending on the details of the calibration procedure) and substantially higher fractions of the more compact Drosophila melanogaster (37%-53%), Caenorhabditis elegans (18%-37%), and Saccharaomyces cerevisiae (47%-68%) genomes.”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Abstract
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In the paper
“These elements share certain properties with ultraconserved elements, but they tend to be longer and less perfectly conserved, and they overlap genes of somewhat different functional categories.”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Almost nine of 10 (88%) known protein-coding exons are overlapped by predicted elements, as well as almost two of three known UTR exons (63% of 5Ј-UTR exons and 64% of 3Ј-UTR exons”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Abstract
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“About 1.31 million conserved elements were predicted for the vertebrate data set, about 472,000 for the insects, about 98,000 for the worms, and about 68,000 for the yeasts.”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Abstract
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In the paper
“Introns of known genes and unannotated (putative intergenic) regions contain significant fractions of conserved bases (3.6% coverage for introns and 2.7% coverage for unannotated regions), but smaller fractions than would be expected by chance.”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Abstract
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The predicted elements also include 42% of the bases in a set of 561 putative RNA genes (see Methods), and 56% of these genes are overlapped by predicted elements”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Abstract
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In the paper
“In all three cases, coding regions show substantially higher coverage than would be expected if conserved elements were distributed randomly, as do UTRs and other mRNAs in worms (but not in insects).”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Abstract
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In the paper
“(If only RNA genes that align syntenically across species are considered, the base-level coverage increases to 65%, about the same as in protein-coding genes).”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Abstract
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
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In the paper
“In insects, worms, and yeasts, genes overlapped by HCEs in coding regions are enriched for some of the same GO categories as in vertebrates, but there are also substantial differences across species groups (Supplemental Table S4).”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Functional enrichment of genes associated with HCEs
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
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In the paper
“The HCEs identified for the other three sets of genomes cover a higher percentage of each reference genome (2.5% in insect, 1.9% in worm, and 8.0% in yeast)”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Highly conserved elements
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In the paper
“As with the vertebrates, the HCEs for the other three species groups are quite long, with lengths ranging from 197 to 5783 bp (mean 627.9 bp) for the insects, 622 to 12646 bp (mean 1889.6 bp) for the worms, and 323 to 4005 bp (mean 973.5 bp) for the yeasts.”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Highly conserved elements
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Indeed, the RNA-editing site in GRIA2, shown in Figure 4, corresponds to an HCE, as do the editing sites in the related genes GRIA3 and GRIA4.”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Functional enrichment of genes associated with HCEs
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Introns and unannotated regions show lower than expected coverage by conserved elements in all three species groups, but still appear to contain substantial numbers of conserved bases.”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
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In the paper
“The fractions of introns and intergenic regions in conserved elements are similar, with introns showing slightly higher fractions in all groups but yeast (where they are few in number).”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Abstract
Strength:plain· not yet calibratedn = 3Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The fractions of HCEs in insects overlapping UTRs are similar to those in vertebrates (6.1% and 15.5% overlap 5Ј and 3Ј UTRs, respectively), but in worm, these fractions are considerably lower (1.9% and 3.7%).”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Highly conserved elements
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In the paper
“The lengths of the predicted elements for all four species groups are approximately geometrically distributed, averaging about 100-120 bp for the vertebrate, insect, and yeast groups and about 270 bp for the less phylogenetically informative worm group.”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Abstract
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In the paper
“Moving from vertebrates to insects and then to worms and to yeasts, in decreasing order of genome size and general biological complexity, a progressively larger fraction of conserved elements can be seen to fall in coding regions and UTRs, and a progressively smaller fraction in introns and unannotated regions (Fig. 3).”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Abstract
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In the paper
“In particular, the fractions of elements in coding regions, UTRs, and other mRNAs tend to increase with score, while the fraction in introns tend to decrease.”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Abstract
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In the paper
“Nevertheless, only 42% of HCEs overlap known exons (36% overlap CDS exons, 9% overlap 5Ј UTR exons, and 16% overlap 3Ј UTR exons), with 19% falling completely in known introns, and another 32% completely in unannotated regions.”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Highly conserved elements
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In the paper
“Here, the 3Ј-UTR HCEs show a statistically significant enrichment for secondary structure (P = 0.02), but the 5Ј-UTR, intronic, and intergenic HCEs (for which the sample sizes are quite small) do not.”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Secondary structure in noncoding HCEs
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In the paper
“A more detailed analysis in vertebrates revealed noticeable differences in the length distributions of the elements associated with different types of annotations; elements in ARs are shortest, on average, those in introns and intergenic regions are slightly longer, those in UTRs are longer still, and those in CDSs are longest (Supplemental Fig. S3).”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Abstract
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In the paper
“These highly conserved elements (HCEs) are like ultraconserved elements (UCEs) (Bejerano et al. 2004b) in that they show extreme evolutionary conservation (defined by some arbitrary threshold), but HCEs tend to be longer than UCEs and tend to have less extreme sequence conservation, due to the length dependency of the log-odds scores.”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Highly conserved elements
What the sources say
- Not matchedcites Bejerano et al. 2004b
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
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- Not matched
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In the paper
“At the base level, coding regions are enriched 22-fold for HCEs, while 3Ј UTRs and 5Ј UTRs are enriched 11-fold and eightfold, respectively.”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Highly conserved elements
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In the paper
“In vertebrates, 18.0% of conserved bases fall in known coding regions (CDSs), 1.1% and 3.6% fall in known 5Ј and 3Ј UTRs, respectively”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Abstract
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In the paper
“and another 5.2% fall in other mRNAs.Another 2.4% fall in other transcribed regions, leaving about 70% unannotated.”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Abstract
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In the paper
“As noted above, 3Ј UTRs account for an unexpectedly large fraction of bases in vertebrate HCEs, and this trend becomes more pronounced as higher scoring subsets of all conserved elements are considered-3Ј UTRs account for 9.6% of bases in the top 5000 elements, 12.5% in the top 1000, and 14.3% in the top 100, compared with 5.6% in all conserved elements (Supplemental Fig. S3).”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > HCEs in the 3Ј UTRs of vertebrate genes
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In the paper
“They are considerably longer on average than elements in the full set (lengths ranged from 318 to 4922 bp, with mean 781.4 bp)”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Highly conserved elements
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In the paper
“FPSs in intronic HCEs are, on average, about the same as those in 3Ј-UTR HCEs, while FPSs in intergenic HCEs are, on average, intermediate between those in 3Ј-and 5Ј-UTR HCEs.”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Secondary structure in noncoding HCEs
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In the paper
“In contrast, 5Ј UTRs are only slightly overrepresented in HCEs (1.5% of bases, compared with 1.1% in all conserved elements), and they are almost absent in the top 100 elements.”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > HCEs in the 3Ј UTRs of vertebrate genes
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In the paper
“In addition, the set of vertebrate HCEs is about 10-fold larger than the set of UCEs and is based on a different set of species (including chicken and Fugu).”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Highly conserved elements
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In the paper
“While most bases in ARs have evolved neutrally (ARs are underrepresented fivefold in conserved elements), some have apparently taken on critical functions that may help to differentiate mammals from ancestral vertebrates (Britten 1997;Jordan et al. 2003;van de Lagemaat et al. 2003).”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Abstract
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- Rests on an assumption: Most bases in mammalian ancestral repeats are neutrally evolving.
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In the paper
“The multiple alignments consisted of blocks of local alignment covering 40.0% of the human genome, 86.9% of D. melanogaster, 43.8% of C. elegans, and 96.6% of S. cerevisiae (Supplemental Table S2).”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Additional information
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In the paper
“Even if redefined such that the HCEs are excluded when computing the CNF pc , the phastCons high-CNF segments overlap 13% of all HCEs and 18% of intronic/intergenic HCEsenrichments of eightfold and 13-fold, respectively.”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Vertebrate HCEs and segments rich in conserved noncoding sequence
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In the paper
“We have carried out a preliminary analysis of a larger set of insect genomes, including draft assemblies of D. ananassae, D. virilis, and D. mojavensis, and found that the total coverage by conserved elements and the fraction of conserved elements in noncoding regions both de-creased somewhat, but did not change dramatically; the general properties of conserved elements and HCEs were essentially”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Discussion
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- The authors state this as an assumption: Coding regions evolve in fundamentally similar ways across species groups, more similar than noncoding regions.
- The authors state this as an assumption: The fraction of sites in coding regions that are conserved is not highly sensitive to the phylogeny.
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In the paper
“These independently defined phastCons high-CNF segments also include 23% of human/rodent ultraconserved elements, a 15-fold enrichment.”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Vertebrate HCEs and segments rich in conserved noncoding sequence
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In the paper
“Peaks in the conservation plot generally correspond to exons and valleys to noncoding regions, but a 158-bp conserved noncoding element can be seen near the 3Ј end of exon 11.”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Functional enrichment
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In the paper
“In addition, the fractions of conserved bases that fall in protein-coding regions are lowest for vertebrates (11%-24%), slightly higher for insects (26%-27%), substantially higher for worms (49%-60%), and highest for yeasts (84%-87%).”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Discussion
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- The authors state this as an assumption: Coding regions evolve in fundamentally similar ways across species groups, more similar than noncoding regions.
- The authors state this as an assumption: The fraction of sites in coding regions that are conserved is not highly sensitive to the phylogeny.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Unlike human/ chicken high-CNF segments, these segments are not significantly depleted for genes, but like human/chicken high-CNF segments, they show a significant enrichment for trans-dev genes.”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Vertebrate HCEs and segments rich in conserved noncoding sequence
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In the paper
“A fourth GAL4-binding site also is reflected by a small bump in the conservation scores (left arrow), as is the promoter itself (right arrow).”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Functional enrichment
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In the paper
“(The 451 sequences mapped perfectly to 561 positions in the genome.)”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Additional information
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In the paper
“On the left, several synonymous substitutions are visible (highlighted bases) and the elevated conservation abruptly ends after the splice site, while on the right, there are fewer synonymous substitutions and the elevated conservation extends into the intron.”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Functional enrichment
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In the paper
“In all three cases, the difference between the distributions is highly statistically significant (P = 8.8 e-66, P = 1.1 e-8, and P = 4.4 e-215, respectively; Wilcoxon rank sum test).”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Functional enrichment
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In the paper
“Stable gene deserts account for only 12% of bases in intergenic regions, yet 53% of the 1578 intergenic HCEs fall within or overlap stable deserts, 4.5 times the expected number.”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > HCEs and gene deserts
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In the paper
“There are 101 phastCons high-CNF segments covering 2.1% of the human genome and averaging 601 kb in length and 13.8% CNF pc .”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Vertebrate HCEs and segments rich in conserved noncoding sequence
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In the paper
“Conversely, 75% of stable deserts include or are overlapped by at least one HCE, while this is true for only 15% of variable deserts.”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > HCEs and gene deserts
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In the paper
“In particular, the fractions of bases in each reference genome that are conserved across related species are smallest for vertebrates (3%-8%), intermediate for worms and insects (18%-37% and 37%-53%, respectively), and largest for yeasts (47%-68%).”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- The authors state this as an assumption: Coding regions evolve in fundamentally similar ways across species groups, more similar than noncoding regions.
- The authors state this as an assumption: The fraction of sites in coding regions that are conserved is not highly sensitive to the phylogeny.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Strong cross-species conservation can be seen in the regulatory region upstream of the promoter, as well as in the protein-coding portion of the gene.”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Functional enrichment
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In the paper
“In contrast, variable gene deserts account for 30% of bases in intergenic regions and only 2.2% of intergenic HCEs fall within or overlap variable deserts.”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > HCEs and gene deserts
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In the paper
“Most groups have used pairwise alignments and simple, percent identity-based methods for identifying conserved elements.”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Abstract
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In the paper
“In addition, most methods (including phylogenetic shadowing) use a sliding window of fixed size, which can be a limitation.”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Abstract
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In the paper
“only the “phylogenetic shadowing” method (Boffelli et al. 2003) (to our knowledge) makes use of the branch lengths of the phylogeny, allows for multiple substitutions per site on single branches of the tree, and considers the “pattern” of substitution”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Abstract
What the sources say
- Not checked — no full text of the sourcecites Boffelli et al. 2003 source
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In the paper
“Our results are, in general, not highly sensitive to the precise level of target coverage used in this calibration procedure (see Supplemental material).”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Abstract
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In the paper
“we constrained the model parameters such that the coverage of known coding regions by predicted conserved elements (i.e., the fraction of coding bases falling in conserved elements) was equivalent in all groups.”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Abstract
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In the paper
“it does not depend on 4d sites being free from selection or being suitable proxies for neutrally evolving sites in general; and as an “unsupervised” learning method (see Methods), it is not dependent on possibly incomplete and/or erroneous annotations.”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Abstract
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In the paper
“Note that the results for worm may be influenced by the difficulty of aligning noncoding regions in C. elegans and C. briggsae and by the limited phylogenetic information in pairwise alignments (see Discussion and Supplemental material).”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Abstract
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In the paper
“but it nevertheless underscores the importance of noncoding regions in the genomes of complex eukaryotes, whose complexity apparently derives not so much from increased numbers of proteincoding genes as from more elaborate mechanisms for gene regulation.”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Abstract
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In the paper
“SCFGs are richer computational models than HMMs, which can accommodate the long distance base pairing that occurs in RNA structures (Durbin et al. 1998).”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Secondary structure in noncoding HCEs
What the sources say
- Not matchedcites Durbin et al. 1998
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
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- Not matched
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In the paper
“Correlations between HCEs and predicted miRNA target sites must be treated cautiously, because they may be artifacts of considering conservation in target-site prediction.”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > HCEs in the 3Ј UTRs of vertebrate genes
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In the paper
“Three groups of known RNA-binding proteins and the mRNAs they bind provide further circumstantial evidence for a connection between HCEs in 3Ј UTRs and post-transcriptional regulation, and moreover (if predictions of target sites are accurate), for a connection with miRNAs.”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > HCEs in the 3Ј UTRs of vertebrate genes
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In the paper
“Note that the fraction of conserved elements in introns and intergenic regions may be underestimated for the twospecies worm data set (see Discussion and Supplemental material).”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Abstract
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In the paper
“The FPS reflects possible (local) stem-pairings within each sequence in a multiple alignment and compensatory substitutions along the branches of the phylogeny, but is designed to avoid biases related to base composition, overall conservation level, and sequence length (see Methods and Supplemental material).”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Secondary structure in noncoding HCEs
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In the paper
“The fraction of HCEs overlapping known exons is somewhat higher than the 23% observed for UCEs (Bejerano et al. 2004b), presumably because of the length depen-dency of the log-odds scores and the tolerance for a small number of substitutions.”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Highly conserved elements
What the sources say
- Not matchedcites Bejerano et al. 2004b
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
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- Not matched
In the paper
“MiR-196 is unusual among known animal miRNAs for its near-perfect complementarity to its HOXB8 target site and for inducing cleavage of the HOXB8 mRNA rather than inhibiting translation (Yekta et al. 2004).”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > HCEs in the 3Ј UTRs of vertebrate genes
What the sources say
- Not checked — no full text of the sourcecites Yekta et al. 2004 source
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In the paper
“In addition, having only two species considerably reduced the amount of phylogenetic information per site, forcing the tuning parameter (expected length) to be increased, and in turn, causing short, conserved elements to tend to be missed, and larger numbers of nonconserved bases to be contained within predicted conserved elements (see Methods).”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Discussion
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In the paper
“No correction for multiple testing was performed, but there were fewer than 1000 individual tests, so P < 5 e-5 can be considered significant.”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Functional enrichment
Strength:plain· not yet calibratedn = 1,000Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Using different window sizes, relaxing the constraints on columns with missing data and using the Kolmogorov-Smirnov test instead of the Wilcoxon test did not produce significant differences in our results.”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Secondary structure
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Similar evidence was found for insect HCEs.”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Discussion
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✗ Based: failsProbably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“More complex parameterizations also increase the danger of converging on biologically uninteresting local maxima of the likelihood function.”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✗ Based: failsProbably not a substantial claim. The paper may give no reason why it holds.
- The authors state this as an assumption: All sites evolve at one of two evolutionary rates: conserved and nonconserved.
- The authors state this as an assumption: The two evolutionary rates are uniform across the genome.
- The authors state this as an assumption: Sites evolve independently conditional on whether they are in conserved or nonconserved regions.
- The authors state this as an assumption: The phylogenetic models for conserved and nonconserved regions have the same branch-length proportions, base compositions, and substitution patterns.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Furthermore, misplacements of alignment gaps may cause regions to appear more or less conserved than they really are.”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Discussion
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As with ultraconserved elements, the reasons for the extreme conservation observed in most vertebrate HCEs remain unknown, but statistical enrichments and individual cases suggest that at least some of these sequences function as cisregulatory binding sites, as RNA genes, in mRNA secondary structures important for RNA editing or post-transcriptional regulation, or as microRNA targets.”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Finally, it is important to note that our entire analysis is conditional on whole-genome alignments produced by the MULTIZ program.”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Discussion
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Some conserved elements are undoubtedly missed because of alignment failures, and even with synteny filtering, other predicted elements are probably spurious in that they are based on alignments of nonorthologous sequence.”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Discussion
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Only exact matches were retained, but many of these genes are short and some tend to match repeats, so some false matches are undoubtedly included in this set.”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Additional information
Strength:boosted· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The individual parameter estimates were fairly consistent and their averages should be close to true genome-wide m.l.e.'s (see Supplemental material).”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > PhastCons
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“This constraint was designed to ensure that predicted conserved elements were supported by similar (minimal) amounts of phylogenetic evidence, taking into consideration differences in phylogenetic information per site.”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Constraints on coverage and smoothness
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Possible biases related to alignment gaps and missing data were avoided by constraining the structures such that alignment columns with >50% gaps or missing data had to fall in nonpairing regions.”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Secondary structure
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These elements tend to be short, e.g., compared with those in 3Ј UTRs, and may fail to be identified as HCEs simply for this reason.”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Discussion
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Note that these graphs change somewhat (but not dramatically) under alternative calibration methods (see Supplemental material).”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Functional enrichment
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“The phylogenetic models in sp and nsp for stem-pairing and nonpairing positions were trained on known RNA structures from Rfam (Griffiths-Jones et al. 2003), but were forced to have equal expected rates of substitution to avoid biases related to conservation level.”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Secondary structure
What the sources say
- Not matchedcites Griffiths-Jones et al. 2003
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
- Not matched
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Together, these factors have probably resulted in an overestimate of the fraction of conserved bases that fall in coding regions (estimated at 49%-60%), and may have resulted in an underestimate of the total fraction conserved (estimated at 18%-37%).”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- The authors state this as an assumption: Coding regions evolve in fundamentally similar ways across species groups, more similar than noncoding regions.
- The authors state this as an assumption: The fraction of sites in coding regions that are conserved is not highly sensitive to the phylogeny.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, HCEs are substantially enriched in stable gene deserts and depleted in variable gene deserts, and most stable deserts have HCEs, while most variable deserts do not.”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > HCEs and gene deserts
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Fragments with sparse data (<1000 sites aligned) were excluded from this procedure, but the amount of data discarded in this way was negligible, and the average parameter estimates can reasonably be said to represent the entire genome-wide data sets.”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > PhastCons
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Our results generally support previous estimates of the fraction of the human genome under selection and the fraction of conserved human bases that fall in noncoding regions, and they allow for an approximate quantitative comparison of these fractions across species groups.”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“For practical reasons, exact maximum likelihood estimates (m.l.e.'s) of free parameters were not obtained for entire genomewide data sets, but instead, the genome-wide alignments were divided into fragments of, at most, about 1 Mb in length (in the coordinate system of the reference genome), and parameters were estimated separately for each fragment.”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > PhastCons
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“To avoid length biases, we did not score whole UTRs, but instead, computed the FPS locally in a sliding window of 150 bp (step size 50 bp).”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Secondary structure
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“In addition, the rate matrix in nsp is a marginalized version of the rate matrix in sp , so that the two models make use of the same nucleotide distribution.”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Secondary structure
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“In addition, treating alignment gaps as missing data ignores an important source of phylogenetic information.”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Discussion
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✗ Based: failsProbably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The phylo-HMM used by phastCons is a fairly rich probabilistic model, but it is clearly not realistic in several respects.”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Discussion
Strength:boosted· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- The authors state this as an assumption: All sites evolve at one of two evolutionary rates: conserved and nonconserved.
- The authors state this as an assumption: The two evolutionary rates are uniform across the genome.
- The authors state this as an assumption: Sites evolve independently conditional on whether they are in conserved or nonconserved regions.
- The authors state this as an assumption: The phylogenetic models for conserved and nonconserved regions have the same branch-length proportions, base compositions, and substitution patterns.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The large degree of divergence between C. elegans and C. briggsae led to low-alignment coverage, and may have created a bias toward alignment of conserved elements in coding rather than noncoding regions (because conserved noncoding regions tend to be shorter on average; hence, harder to align.)”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Nevertheless, alternative calibration methods-based on full maximumlikelihood parameter estimation, estimation of neutral rates from fourfold degenerate sites, and alternative coverage targets in coding regions-have led to generally similar results (see Supplemental material), and certain basic conclusions appear to be fairly robust.”
§ Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- The authors state this as an assumption: Coding regions evolve in fundamentally similar ways across species groups, more similar than noncoding regions.
- The authors state this as an assumption: The fraction of sites in coding regions that are conserved is not highly sensitive to the phylogeny.
The authors state this as an assumption.
The tree topologies for the vertebrate, insect, worm, and yeast data sets are known.
“The tree topologies were assumed to be known (see Supplemental material).”
The paper relies on this without support.
The primary reason for cross-species sequence conservation is negative (purifying) selection.
“the primary reason for cross-species sequence conservation is believed to be negative (purifying) selection.”
The paper relies on this without support.
Most bases in mammalian ancestral repeats are neutrally evolving.
“which are believed, for the most part, to be neutrally evolving”
The authors state this as an assumption.
Coding regions evolve in fundamentally similar ways across species groups, more similar than noncoding regions.
“Our approach of holding fixed the coverage of coding regions by predicted conserved elements assumes that coding regions evolve in fundamentally similar ways across species groups (more similar than noncoding regions), and that the fraction of sites in coding regions that are conserved is not highly sensitive to the phylogeny.”
The authors state this as an assumption.
The fraction of sites in coding regions that are conserved is not highly sensitive to the phylogeny.
“Our approach of holding fixed the coverage of coding regions by predicted conserved elements assumes that coding regions evolve in fundamentally similar ways across species groups (more similar than noncoding regions), and that the fraction of sites in coding regions that are conserved is not highly sensitive to the phylogeny.”
The authors state this as an assumption.
All sites evolve at one of two evolutionary rates: conserved and nonconserved.
“The assumptions that all sites evolve at one of two evolutionary rates (conserved and nonconserved), that these rates are uniform across the genome, that sites evolve independently conditional on whether they are in conserved or nonconserved regions, and that the phylogenetic models for conserved and nonconserved regions have the same branch-length proportions, base compositions, and substitution”
The authors state this as an assumption.
The two evolutionary rates are uniform across the genome.
“The assumptions that all sites evolve at one of two evolutionary rates (conserved and nonconserved), that these rates are uniform across the genome, that sites evolve independently conditional on whether they are in conserved or nonconserved regions, and that the phylogenetic models for conserved and nonconserved regions have the same branch-length proportions, base compositions, and substitution”
The authors state this as an assumption.
Sites evolve independently conditional on whether they are in conserved or nonconserved regions.
“The assumptions that all sites evolve at one of two evolutionary rates (conserved and nonconserved), that these rates are uniform across the genome, that sites evolve independently conditional on whether they are in conserved or nonconserved regions, and that the phylogenetic models for conserved and nonconserved regions have the same branch-length proportions, base compositions, and substitution”
The authors state this as an assumption.
The phylogenetic models for conserved and nonconserved regions have the same branch-length proportions, base compositions, and substitution patterns.
“The assumptions that all sites evolve at one of two evolutionary rates (conserved and nonconserved), that these rates are uniform across the genome, that sites evolve independently conditional on whether they are in conserved or nonconserved regions, and that the phylogenetic models for conserved and nonconserved regions have the same branch-length proportions, base compositions, and substitution”
The paper relies on this without support.
HCEs in coding regions are not expected to have extensive secondary structure.
“We also computed FPSs for HCEs in coding regions, which are not expected to have extensive secondary structure.”
The authors state this as an assumption.
Conserved and nonconserved sites are drawn independently from the distributions associated with c and n, respectively.
“Assuming conserved and nonconserved sites are drawn independently from the distributions associated with c and n , respectively, L min is given by:”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“One of the major revelations of comparative genomics has been the discovery of regions of the genome falling well outside protein-coding genes that nonetheless exhibit considerable levels of conservation across evolutionary time”
From Bayesian Detection of Convergent Rate Changes of Conserved Noncoding Elements on Phylogenetic Trees (2019) · cites this paper as Siepel et al. 2005
In the citing paper
“Genomic sequence conservation is one such criterion that indicates the relevance of a stretch of DNA, as it has been maintained by natural selection.”
From Inferring and perturbing cell fate regulomes in human brain organoids (2023) · cites this paper as [29]
In the citing paper
“Various comparative genomics resources, including PhyloP (Pollard et al., 2010), PhastCons (Siepel et al., 2005), and GERP++ (Davydov et al., 2010), showed our top loci to have similar properties regardless of the extent of pleiotropy.”
From Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders (2019) · cites this paper as Siepel et al., 2005
In the citing paper
“We identified a collection of eutherian conserved elements that cover 104 Mb (3.7%) of the human genome, using the phylo-HMM approach 14 ; ,29% of them overlap protein-coding sequence (Supplementary Data).”
From Genome of the marsupial Monodelphis domestica reveals innovation in non-coding sequences (2007) · cites this paper as [14]
In the citing paper
“However, these cases together comprise only a trivial fraction of the CNEs in the human genome.”
From Genome of the marsupial Monodelphis domestica reveals innovation in non-coding sequences (2007) · cites this paper as [14]
In the citing paper
“Individual instances of CNEs derived from transposable elements have been described previously 14,94,95 .”
From Genome of the marsupial Monodelphis domestica reveals innovation in non-coding sequences (2007) · cites this paper as [14]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Conflicting shares of conserved bases in known 3′ UTRs
MajorThe paper gives two different shares for known 3′ UTRs among all vertebrate conserved bases: 3.6% and 5.6%. Both statements describe the full set of conserved elements, rather than different top-scoring subsets.
“3Ј UTRs account for 9.6% of bases in the top 5000 elements, 12.5% in the top 1000, and 14.3% in the top 100, compared with 5.6% in all conserved elements”
“In vertebrates, 18.0% of conserved bases fall in known coding regions (CDSs), 1.1% and 3.6% fall in known 5Ј and 3Ј UTRs, respectively, and another 5.2% fall in other mRNAs.”
Citations
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Research works printed but not linked: 5
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Cited by
Sorted by citations
ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data
Wang, K., Li, M., & Hakonarson, H. H. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq603 · Cited by 14,724
“This annotation database contains multiple alignments of 44 vertebrate species and measurements of evolutionary conservation using two methods, phastCons (18) and phyloP (19) on the human genome (UCSC build version: hg18).”
MethodA general framework for estimating the relative pathogenicity of human genetic variants
Kircher, M., Witten, D. M., Jain, P., O'Roak, B. J., Cooper, G. M., & Shendure, J. (2014) · Nature Genetics · doi:10.1038/ng.2892 · Cited by 6,183
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“We used the precomputed, nucleotide-level calculations of evolutionary selection provided by the phastCons algorithm (Siepel et al. 2005).”
MethodChromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals
Guttman, M., Amit, I., Garber, M., French, C., Lin, M. F., Feldser, D., Huarte, M., Zuk, O., Carey, B. W., Cassady, J. P., et al. (2009) · Nature · doi:10.1038/nature07672 · Cited by 4,098
CADD: predicting the deleteriousness of variants throughout the human genome
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“PhyloP (16), PhastCons (17), GERP++ (18)), different tracks from the UCSC genome browser (19) as well as flat files of epigenetic information from the ENCODE and NIH RoadMap projects.”
REVEL: An Ensemble Method for Predicting the Pathogenicity of Rare Missense Variants
Ioannidis, N. M., Rothstein, J. H., Pejaver, V., Middha, S., McDonnell, S. K., Baheti, S., Musolf, A., Li, Q., Holzinger, E., Karyadi, D., et al. (2016) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2016.08.016 · Cited by 2,908
Mapping and analysis of chromatin state dynamics in nine human cell types
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Predicting effects of noncoding variants with deep learning–based sequence model
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Self-citationGenome sequence, comparative analysis and haplotype structure of the domestic dog
members, B. S. P., Lindblad-Toh, K., Wade, C. M., Mikkelsen, T. S., Karlsson, E. K., Jaffe, D. B., Kamal, M., Clamp, M., Chang, J. L., Kulbokas, E. J., et al. (2005) · Nature · doi:10.1038/nature04338 · Cited by 2,568
“We note that the 204 regions include nearly all of the recently identified clusters of conserved elements between distantly related vertebrates such as chicken and pufferfish 55,59–62 .”
BackgroundA Long Noncoding RNA Controls Muscle Differentiation by Functioning as a Competing Endogenous RNA
Cesana, M., Cacchiarelli, D., Legnini, I., Santini, T., Sthandier, O., Chinappi, M., Tramontano, A., & Bozzoni, I. (2011) · Cell · doi:10.1016/j.cell.2011.09.028 · Cited by 2,554
The microRNA.org resource: targets and expression
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“Specifically, to filter out less-conserved predicted target sites, we use the PhastCons conservation score, which measures the evolutionary conservation of sequence blocks across multiple vertebrates using a phylogenetic hidden Markov model (21).”
MethodMattick, J. S., & Makunin, I. V. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddl046 · Cited by 2,546
“The extent of non-coding sequence conservation in mammals is also much higher than that of protein-coding sequences (202,206), perhaps as high as 10% by some estimates (207).”
BackgroundUsing native and syntenically mapped cDNA alignments to improve de novo gene finding
Stanke, M., Diekhans, M., Baertsch, R., & Haussler, D. (2008) · Bioinformatics · doi:10.1093/bioinformatics/btn013 · Cited by 2,605
“Further, in the de novo category, we used hints of type CDSpart created from the PHASTCONS conserved elements predictions ( Siepel et al. (2005) ) using the script phastconsDB2hints.pl in the AUGUSTUS distribution.”
MethodSelf-citationControl of Developmental Regulators by Polycomb in Human Embryonic Stem Cells
Lee, T. I., Jenner, R. G., Boyer, L. A., Guenther, M. G., Levine, S. S., Kumar, R., Chevalier, B. S., Johnstone, S. E., Cole, M. F., Isono, K., et al. (2006) · Cell · doi:10.1016/j.cell.2006.02.043 · Cited by 2,296
“Using entries from the PhastCons database of conserved elements (Siepel et al., 2005), we found that SUZ12 occupancy of highly conserved elements was highly significant (using highly conserved elements with a LoD conservation score of 100 or better, the p-value for significances was less than 10 (85)).”
BackgroundMethodInfluentialGalaxy: a platform for interactive large-scale genome analysis.Preprint
Giardine, B., Riemer, C., Hardison, R., Burhans, R. C., Elnitski, L., Shah, P., Zhang, Y., Blankenberg, D., Albert, I., Taylor, J., et al. (2005) · Genome Research · doi:10.1101/gr.4086505 · Cited by 2,217
“Other examples of efforts integrating various data sources and analysis tools include ISYS ( Siepel et al. 2001 ) and the Biology Workbench (Subramaniam 1998).”
MethodSelf-citationA high-coverage genome sequence from an archaic denisovan individual
Meyer, M., Kircher, M., Gansauge, M.-T., Li, H., Racimo, F., Mallick, S., Schraiber, J. G., Jay, F., Prüfer, K., de Filippo, C., et al. (2012) · Science · doi:10.1126/science.1224344 · Cited by 1,967
The genomic basis of adaptive evolution in threespine sticklebacks
Jones, F. C., Grabherr, M. G., Chan, Y. F., Russell, P. H., Mauceli, E., Johnson, J., Swofford, R., Pirun, M., Zody, M. C., White, S. J., et al. (2012) · Nature · doi:10.1038/nature10944 · Cited by 1,793
Identifying a High Fraction of the Human Genome to be under Selective Constraint Using GERP++
Davydov, E. V., Goode, D. L., Sirota, M., Cooper, G. M., Sidow, A., & Batzoglou, S. (2010) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1001025 · Cited by 1,757
“We compared the GERP ++ constrained element predictions in placental mammals (see Methods) to phastCons [4], the leading generative model-based tool.”
MethodResultA genomic mutational constraint map using variation in 76,156 human genomes
Chen, S., Francioli, L. C., Goodrich, J. K., Collins, R. L., Kanai, M., Wang, Q., Alföldi, J., Watts, N. A., Vittal, C., Gauthier, L. D., et al. (2024) · Nature · doi:10.1038/s41586-023-06045-0 · Cited by 1,727
The UCSC Genome Browser Database: update 2006
Hinrichs, A. S. (2006) · Nucleic Acids Research · doi:10.1093/nar/gkj144 · Cited by 1,646
Self-citationChIP-seq accurately predicts tissue-specific activity of enhancers
Visel, A., Blow, M. J., Li, Z., Zhang, T., Akiyama, J. A., Holt, A., Plajzer-Frick, I., Shoukry, M., Wright, C., Chen, F., et al. (2009) · Nature · doi:10.1038/nature07730 · Cited by 1,639
Comprehensive modeling of microRNA targets predicts functional non-conserved and non-canonical sites
Betel, D., Koppal, A., Agius, P., Sander, C., & Leslie, C. (2010) · Genome Biology · doi:10.1186/gb-2010-11-8-r90 · Cited by 1,592
“We used phastCons scores [38] for target site conservation, which measures the conservation of nucleotide positions across multiple vertebrates.”
MethodA novel class of small RNAs bind to MILI protein in mouse testes
Aravin, A., Gaidatzis, D., Pfeffer, S., Lagos-Quintana, M., Landgraf, P., Iovino, N., Morris, P., Brownstein, M. J., Kuramochi-Miyagawa, S., Nakano, T., et al. (2006) · Nature · doi:10.1038/nature04916 · Cited by 1,516
Robertson, G., Hirst, M., Bainbridge, M., Bilenky, M., Zhao, Y., Zeng, T., Euskirchen, G., Bernier, B., Varhol, R., Delaney, A., et al. (2007) · Nature Methods · doi:10.1038/nmeth1068 · Cited by 1,454
“Because evolutionary conservation is a useful, though incomplete, indication that a sequence may be functiona”
BackgroundGenomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders
Lee, P. H., Anttila, V., Won, H., Feng, Y.-C. A., Rosenthal, J., Zhu, Z., Tucker-Drob, E. M., Nivard, M. G., Grotzinger, A. D., Posthuma, D., et al. (2019) · Cell · doi:10.1016/j.cell.2019.11.020 · Cited by 1,381
“Various comparative genomics resources, including PhyloP (Pollard et al., 2010), PhastCons (Siepel et al., 2005), and GERP++ (Davydov et al., 2010), showed our top loci to have similar properties regardless of the extent of pleiotropy.”
BackgroundEvolution and impact of subclonal mutations in chronic lymphocytic leukemia
Landau, D. A., Carter, S. L., Stojanov, P., McKenna, A., Stevenson, K., Lawrence, M. S., Sougnez, C., Stewart, C., Sivachenko, A., Wang, L., et al. (2013) · Cell · doi:10.1016/j.cell.2013.01.019 · Cited by 1,379
Genome-wide analysis of estrogen receptor binding sites
Carroll, J. S., Meyer, C. A., Song, J. S., Li, W., Geistlinger, T., Eeckhoute, J., Brodsky, A. S., Keeton, E. K., Fertuck, K. C., Hall, G., et al. (2006) · Nature Genetics · doi:10.1038/ng1901 · Cited by 1,397
“The 3,665 estrogen receptor ChIP regions were aligned at their centers and uniformly expanded to 3,000 bp in each direction, and phastCon”
MethodA map of the cis-regulatory sequences in the mouse genome
Shen, Y., Yue, F., McCleary, D. F., Ye, Z., Edsall, L., Kuan, S., Wagner, U., Dixon, J., Lee, L., Lobanenkov, V. V., et al. (2012) · Nature · doi:10.1038/nature11243 · Cited by 1,361
Transposable elements and the evolution of regulatory networks
Feschotte, C. (2008) · Nature Reviews Genetics · doi:10.1038/nrg2337 · Cited by 1,379
“Cross-species genome alignments have revealed an abundance of CNEs in species as diverse as dipteran insects, nematodes, yeasts, grasses and crucifer”
Faircloth, B. C., McCormack, J. E., Crawford, N. G., Harvey, M. G., Brumfield, R. T., & Glenn, T. C. (2012) · Systematic Biology · doi:10.1093/sysbio/sys004 · Cited by 1,303
“2011), invertebrates, and fungi (Siepel et al. 2005); species separated for hundreds of millions of years.”
BackgroundTranscriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder
Gandal, M. J., Zhang, P., Hadjimichael, E., Walker, R. L., Chen, C., Liu, S., Won, H., van Bakel, H., Varghese, M., Wang, Y., et al. (2018) · Science · doi:10.1126/science.aat8127 · Cited by 1,247
“DE ncRNAs were further annotated for tissue-specificity using GTEx v6 data (10, 82), evolutionary conservation using phyloP and phastCons scores (92, 93), and exonlevel selective constraint via CDTS (27).”
Identification of Functional Elements and Regulatory Circuits by Drosophila modENCODE
Roy, S., Ernst, J., Kharchenko, P. V., Kheradpour, P., Nègre, N., Eaton, M. L., Landolin, J. M., Bristow, C. A., Ma, L., Lin, M. F., et al. (2010) · Science · doi:10.1126/science.1198374 · Cited by 1,242
Self-citationObesity-associated variants within FTO form long-range functional connections with IRX3
Smemo, S., Tena, J. J., Kim, K.-H., Gamazon, E. R., Sakabe, N. J., Gómez-Marín, C., Aneas, I., Credidio, F. L., Sobreira, D. R., Wasserman, N. F., et al. (2014) · Nature · doi:10.1038/nature13138 · Cited by 1,219
A Common MUC5B Promoter Polymorphism and Pulmonary Fibrosis
Seibold, M. A., Wise, A. L., Speer, M. C., Steele, M. P., Brown, K. M., Loyd, J. E., Fingerlin, T. E., Zhang, W., Guðmundsson, G., Groshong, S. D., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1013660 · Cited by 1,235
VISTA Enhancer Browser—a database of tissue-specific human enhancers
Visel, A., Minovitsky, S., Dubchak, I., & Pennacchio, L. A. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkl822 · Cited by 1,080
“With the availability of whole genome sequences for a growing number of vertebrates and the concurrent emergence of advanced comparative genomic tools (7,8), it is now possible to predict the location of possible enhancers on a genome-wide scale with a specificity that makes their characterization by in vivo assays fe…”
BackgroundConserved Function of lincRNAs in Vertebrate Embryonic Development despite Rapid Sequence Evolution
Ulitsky, I., Shkumatava, A., Jan, C. H., Sive, H. L., & Bartel, D. P. (2011) · Cell · doi:10.1016/j.cell.2011.11.055 · Cited by 1,197
“%) distinct zebrafish lincRNAs A D CB (A) Conservation levels of lincRNA and protein-coding introns and exons, computed using phastCons (Siepel et al., 2005) applied to the 8-way whole-genome alignment.”
BackgroundMethodInfluentialBenchmark and integration of resources for the estimation of human transcription factor activities
Garcia-Alonso, L., Holland, C. H., Ibrahim, M. M., Turei, D., & Saez-Rodriguez, J. (2019) · Genome Research · doi:10.1101/gr.240663.118 · Cited by 1,122
A high-resolution map of human evolutionary constraint using 29 mammals
Broad Institute Sequencing Platform and Whole Genome Assembly Team, Lindblad-Toh, K., Baylor College of Medicine Human Genome Sequencing Center Sequencing Team, Genome Institute at Washington University, Garber, M., Zuk, O., Lin, M. F., Parker, B. J., Washietl, S., Kheradpour, P., et al. (2011) · Nature · doi:10.1038/nature10530 · Cited by 1,108
“Elements previously detected using five vertebrates 17 also detect a larger fraction of the genome (~4.1%), but only cover 45% of the mammalian elements detected here, suggesting a large fraction of our elements are mammalian-specific.”
InfluentialSelf-citationComparative genomics reveals insights into avian genome evolution and adaptation
Zhang, G., Li, C., Li, Q., Li, B., Larkin, D. M., Lee, C., Storz, J. F., Antunes, A., Greenwold, M. J., Meredith, R. W., et al. (2014) · Science · doi:10.1126/science.1251385 · Cited by 1,055
“SM Text 4 Selective constraints on functional elements Detecting highly conserved elements (HCEs) PhastCons (45) is a widely-used program to identify highly conserved elements (HCEs) based on the multiple-genome sequence alignments.”
BackgroundInfluentialSelf-citationDiscovery and characterization of chromatin states for systematic annotation of the human genome
Ernst, J., & Kellis, M. (2010) · Nature Biotechnology · doi:10.1038/nbt.1662 · Cited by 1,075
The Imprinted H19 LncRNA Antagonizes Let-7 MicroRNAs
Kallen, A. N., Zhou, X., Xu, J., Qiao, C., Ma, J., Yan, L., Lu, L., Liu, C., Yi, J.-S., Zhang, H., et al. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.08.027 · Cited by 1,068
“After defining a conservation score threshold of 0.57 (Siepel et al., 2005), the sites at positions 1244 and 750 are well and moderately conserved with average conservation scores of 0.75 and 0.64, respectively.”
BackgroundMethodInfluentialInitial impact of the sequencing of the human genome
Lander, E. S. (2011) · Nature · doi:10.1038/nature09792 · Cited by 1,044
Base-Resolution Analysis of 5-Hydroxymethylcytosine in the Mammalian Genome
Yu, M., Hon, G. C., Szulwach, K. E., Song, C., Zhang, L., Kim, A., Li, X., Dai, Q., Shen, Y., Park, B., et al. (2012) · Cell · doi:10.1016/j.cell.2012.04.027 · Cited by 1,050
Analysis of the Vertebrate Insulator Protein CTCF-Binding Sites in the Human Genome
Kim, T. H., Abdullaev, Z., Smith, A. D., Ching, K. A., Loukinov, D. I., Green, R. D., Zhang, M. Q., Lobanenkov, V. V., & Ren, B. (2007) · Cell · doi:10.1016/j.cell.2006.12.048 · Cited by 1,022
“Third, we examined a multiple species sequence alignment score (PhastCon) for each CTCF-binding site (Siepel et al., 2005) to determine their sequence conservation.”
Dilated cardiomyopathy: the complexity of a diverse genetic architecture
Hershberger, R. E., Hedges, D. J., & Morales, A. (2013) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2013.105 · Cited by 1,036
PlantRegMap: charting functional regulatory maps in plants
Tian, F., Yang, D.-C., Meng, Y.-Q., Jin, J., & Gao, G. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz1020 · Cited by 1,018
“Following the established protocols (12,31) and an assessment of the LASTZ (32) parameters (Supplementary Figure S1 and Supplementary Text), we further generated 63 multiple genome alignments using each species as a reference and then detected evolutionary constraints (Figure 2C and Supplementary Text).”
MethodAn atlas of human long non-coding RNAs with accurate 5′ ends
Hon, C.-C., Ramilowski, J. A., Harshbarger, J., Bertin, N., Rackham, O. J. L., Gough, J., Denisenko, E., Schmeier, S., Poulsen, T. M., Severin, J., et al. (2017) · Nature · doi:10.1038/nature21374 · Cited by 1,007
An RNA gene expressed during cortical development evolved rapidly in humans
Pollard, K. S., Salama, S. R., Lambert, N., Lambot, M.-A., Coppens, S., Pedersen, J. S., Katzman, S., King, B., Onodera, C., Siepel, A., et al. (2006) · Nature · doi:10.1038/nature05113 · Cited by 1,005
Self-citationCommon genetic variants on 5p14.1 associate with autism spectrum disorders
Wang, K., Zhang, H., Ma, D., Bucan, M., Glessner, J. T., Abrahams, B. S., Salyakina, D., Imielinski, M., Bradfield, J. P., Sleiman, P. M. A., et al. (2009) · Nature · doi:10.1038/nature07999 · Cited by 989
The genomic substrate for adaptive radiation in African cichlid fish
Brawand, D., Wagner, C. E., Li, Y., Malinsky, M., Keller, I., Fan, S., Simakov, O., Ng, A. Y. J., Lim, Z. W., Bezault, É., et al. (2014) · Nature · doi:10.1038/nature13726 · Cited by 986
Evolution of Darwin’s finches and their beaks revealed by genome sequencing
Lamichhaney, S., Berglund, J., Almén, M. S., Maqbool, K., Grabherr, M. G., Barrio, Á. M., Promerová, M., Rubin, C., Wang, C., Zamani, N., et al. (2015) · Nature · doi:10.1038/nature14181 · Cited by 993
Liu, X., Wu, C., Li, C., & Boerwinkle, E. (2015) · Human Mutation · doi:10.1002/humu.22932 · Cited by 977
“, 2015]; two conservation scores: 2× phastCons [Siepel et al., 2005], and allele frequencies from the UK10K cohorts [UK10K Consortium et al.”
BackgroundThe evolution of lncRNA repertoires and expression patterns in tetrapods
Necsulea, A., Soumillon, M., Warnefors, M., Liechti, A., Daish, T., Zeller, U., Baker, J. C., Grützner, F., & Kaessmann, H. (2014) · Nature · doi:10.1038/nature12943 · Cited by 984
Integrative Analysis of the Caenorhabditis elegans Genome by the modENCODE Project
Gerstein, M., Lu, Z. J., Nostrand, E. L. V., Cheng, C., Arshinoff, B. I., Liu, T., Yip, K. Y.-L., Robilotto, R., Rechtsteiner, A., Ikegami, K., et al. (2010) · Science · doi:10.1126/science.1196914 · Cited by 973
Self-citationTranscriptional Regulatory Elements in the Human Genome
Maston, G. A., Evans, S. K., & Green, M. R. (2006) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev.genom.7.080505.115623 · Cited by 937
“A number of programs have been developed to perform such analyses, such as FootPrinter (21) and PhastCons (165).”
A Large Fraction of Extragenic RNA Pol II Transcription Sites Overlap Enhancers
De Santa, F., Barozzi, I., Mietton, F., Ghisletti, S., Polletti, S., Tusi, B. K., Muller, H., Ragoussis, J., Wei, C.-L., & Natoli, G. (2010) · PLoS Biology · doi:10.1371/journal.pbio.1000384 · Cited by 934
“mammals [62] to measure the degree of conservation in the”
BackgroundCummins, J. M., He, Y., Leary, R. J., Pagliarini, R., Diaz, L. A., Sjoblom, T., Barad, O., Bentwich, Z., Szafranska, A. E., Labourier, E., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0511155103 · Cited by 744
Genetic drift, selection and the evolution of the mutation rate
Lynch, M., Ackerman, M. S., Gout, J.-F., Long, H., Sung, W., Thomas, W. K., & Foster, P. L. (2016) · Nature Reviews Genetics · doi:10.1038/nrg.2016.104 · Cited by 911
Babiarz, J., Ruby, J. G., Wang, Y., Bartel, D. P., & Blelloch, R. H. (2008) · Genes & Development · doi:10.1101/gad.1705308 · Cited by 964
“Small RNAs play a central role in embryonic stem (ES) cells (Stadler and Ruohola-Baker 2008).”
BackgroundThe UCSC genome browser and associated tools
Kuhn, R. M., Haussler, D., & Kent, W. J. (2013) · Briefings in Bioinformatics · doi:10.1093/bib/bbs038 · Cited by 883
“It also shows results from the phastCons and phyloP [23, 24] algorithms that compute conservation scores for each basepair in the genome based on those alignments.”
MethodSelf-citationGenomic variant annotation and prioritization with ANNOVAR and wANNOVAR
Yang, H., & Wang, K. (2015) · Nature Protocols · doi:10.1038/nprot.2015.105 · Cited by 846
“Region-based annotation can be useful when we want to know whether the variants overlap with certain regions of interest, such as conserved genomic elements 28 , cytogenetic bands, microRNA target sites 29 and Encyclopedia of DNA Elements (ENCODE)-annotated regions 30 .”
BackgroundJagadeesh, K. A., Wenger, A. M., Berger, M. J., Guturu, H., Stenson, P. D., Cooper, D. N., Bernstein, J. A., & Bejerano, G. (2016) · Nature Genetics · doi:10.1038/ng.3703 · Cited by 852
Self-citationWhole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder
C Yuen, R. K., Merico, D., Bookman, M., L Howe, J., Thiruvahindrapuram, B., Patel, R. V., Whitney, J., Deflaux, N., Bingham, J., Wang, Z., et al. (2017) · Nature Neuroscience · doi:10.1038/nn.4524 · Cited by 844
“…55 and internal Complete Genomics control databases), genomic conservation (UCSC PhyloP and phastCons for placental mammals and 100 vertebrates 56 ), variant impact predictors (SIFT 57 , PolyPhen2 58 , Mutation Assessor 59 and CADD 60 ) and implication in human genetic disorders (Human…”
Anchored Hybrid Enrichment for Massively High-Throughput Phylogenomics
Lemmon, A. R., Emme, S. A., & Lemmon, E. M. (2012) · Systematic Biology · doi:10.1093/sysbio/sys049 · Cited by 837
“Highly conserved regions of the genome have been discovered in insects, worms, and yeast as well as a diverse set of vertebrates (Glazov et al. 2005; Siepel et al. 2005; Stephen et al. 2008; Wang et al. 2009; Janes et al. 2010) and could easily be used in probe design as in the present study.”
BackgroundPPARγ and C/EBP factors orchestrate adipocyte biology via adjacent binding on a genome-wide scalePreprint
Lefterova, M. I., Zhang, Y., Steger, D. J., Schupp, M., Schug, J., Cristancho, A. G., Feng, D., Zhuo, D. X., Stoeckert, C. J., Liu, X. S., et al. (2008) · Genes & Development · doi:10.1101/gad.1709008 · Cited by 826
“In contrast, expression profiling studies during adipocyte differentiation and following PPAR ligand treatment suggest that hundreds of genes may be regulated by PPAR (Perera et al. 2006; Sears et al. 2007; Nakachi et al. 2008).”
BackgroundThe Cellular and Molecular Landscapes of the Developing Human Central Nervous System
Silbereis, J. C., Pochareddy, S., Zhu, Y., Li, M., & Sestan, N. (2016) · Neuron · doi:10.1016/j.neuron.2015.12.008 · Cited by 818
Transposable elements have rewired the core regulatory network of human embryonic stem cells
Kunarso, G., Chia, N., Jeyakani, J., Hwang, C., Lu, X., Chan, Y.-S., Ng, H., & Bourque, G. (2010) · Nature Genetics · doi:10.1038/ng.600 · Cited by 777
“Finally, for the in silico analysis, we identified the human binding regions that overlap the 28-Way PhastCons Elements trac”
Major Histocompatibility Complex Genomics and Human Disease
Trowsdale, J., & Knight, J. C. (2013) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-091212-153455 · Cited by 783
“Vertebrate conserved elements are shown based on analysis of 46 species with prediction using PhastCons (107) (light brown).”
Structural imprints in vivo decode RNA regulatory mechanisms
Spitale, R. C., Flynn, R. A., Zhang, Q. C., Crisalli, P., Lee, B., Jung, J., Kuchelmeister, H. Y., Batista, P. J., Torre, E. A., Kool, E. T., et al. (2015) · Nature · doi:10.1038/nature14263 · Cited by 760
Functionality or transcriptional noise? Evidence for selection within long noncoding RNAsPreprint
Ponjavic, J., Ponting, C. P., & Lunter, G. A. (2007) · Genome Research · doi:10.1101/gr.6036807 · Cited by 731
“Multispecies conserved sequences (MCSs) (Siepel et al. 2005) for assembly mm5 were obtained from the UCSC Browser Database (Hinrichs et al.”
MethodLong noncoding RNAs in mouse embryonic stem cell pluripotency and differentiationPreprint
Dinger, M. E., Amaral, P., Mercer, T. R., Pang, K. C., Bruce, S. J., Gardiner, B., Askarian-Amiri, M., Ru, K., Soldà, G., Simons, C., et al. (2008) · Genome Research · doi:10.1101/gr.078378.108 · Cited by 753
“It has been previously shown that phastCons elements in noncoding sequences are enriched for predicted RNA secondary structures (Siepel et al. 2005).”
BackgroundGenome-wide transcription and the implications for genomic organization
Kapranov, P., Willingham, A. T., & Gingeras, T. (2007) · Nature Reviews Genetics · doi:10.1038/nrg2083 · Cited by 735
“The availability of various maps of different functional elements, combined with evolutionary conservation scores for individual base pair”
BackgroundCistrome: an integrative platform for transcriptional regulation studies
Liu, T., Ortiz, J. A., Taing, L., Meyer, C. A., Lee, B. T. K., Zhang, Y., Shin, H., Wong, S. S., Ma, J., Lei, Y., et al. (2011) · Genome biology · doi:10.1186/gb-2011-12-8-r83 · Cited by 705
“In Cistrome, the ‘ Conservation Plot ’ tool can take one or more cistromes in BED files as input, and use UCSC PhastCons conservation scores [20] to produce a figure showing the average conservation score profiles around the peak centers (Figure 2d).”
MethodAn integrated software system for analyzing ChIP-chip and ChIP-seq data
Ji, H., Jiang, H., Ma, W., Johnson, D. S., Myers, R., & Wong, W. H. (2008) · Nature Biotechnology · doi:10.1038/nbt.1505 · Cited by 722
“To characterize the conservation level of the binding regions, CisGenome allows users to first choose a t such that x percent of the whole genome has a phastCon”
Genome of the marsupial Monodelphis domestica reveals innovation in non-coding sequences
Broad Institute Genome Sequencing Platform, Mikkelsen, T. S., Broad Institute Whole Genome Assembly Team, Wakefield, M. J., Aken, B., Amemiya, C. T., Chang, J. L., Duke, S., Garber, M., Gentles, A. J., et al. (2007) · Nature · doi:10.1038/nature05805 · Cited by 711
The relationship between non‐protein‐coding DNA and eukaryotic complexity
Taft, R. J., Pheasant, M., & Mattick, J. S. (2007) · BioEssays · doi:10.1002/bies.20544 · Cited by 731
Defining functional DNA elements in the human genome
Kellis, M., Wold, B. J., Snyder, M. P., Bernstein, B., Kundaje, A. B., Marinov, G. K., Ward, L. D., Birney, E., Crawford, G. E., Dekker, J., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1318948111 · Cited by 724
A high-resolution map of transcription in the yeast genome
David, L., Huber, W. K., Granovskaia, M., Toedling, J., Palm, C. J., Bofkin, L., Jones, T., Davis, R. W., & Steinmetz, L. M. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0601091103 · Cited by 706
Sumazin, P., Yang, X., Chiu, H., Chung, W., Iyer, A. P., Llobet‐Navàs, D., Rajbhandari, P., Bansal, M., Guarnieri, P., Silva, J., et al. (2011) · Cell · doi:10.1016/j.cell.2011.09.041 · Cited by 695
A Highly Conserved Program of Neuronal Microexons Is Misregulated in Autistic Brains
Irimia, M., Weatheritt, R. J., Ellis, J. D., Parikshak, N. N., Gonatopoulos-Pournatzis, T., Babor, M., Quesnel-Vallières, M., Tapial, J., Raj, B., O’Hanlon, D., et al. (2014) · Cell · doi:10.1016/j.cell.2014.11.035 · Cited by 693
“To investigate the conservation of exonic sequences and their flanking intronic regions (150 nucleotides upstream and downstream of the exon), we used human phastCons (Siepel et al., 2005) data from alignments of 46 placental mammals (46way.”
MethodWang, Q., Li, W., Liu, X. S., Carroll, J. S., Jänne, O. A., Keeton, E. K., Chinnaiyan, A. M., Pienta, K. J., & Brown, M. A. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.05.041 · Cited by 689
Chromatin structure analyses identify miRNA promotersPreprint
Ozsolak, F., Poling, L. L., Wang, Z., Liu, H., Liu, X., Roeder, R. G., Zhang, X., Song, J. S., & Fisher, D. E. (2008) · Genes & Development · doi:10.1101/gad.1706508 · Cited by 736
“lutionary conservation scores (Siepel et al. 2005) (C) are shown at miRNA promoters.”
BackgroundTHE QTN PROGRAM AND THE ALLELES THAT MATTER FOR EVOLUTION: ALL THAT'S GOLD DOES NOT GLITTER
Rockman, M. V. (2011) · Evolution · doi:10.1111/j.1558-5646.2011.01486.x · Cited by 679
“…the GWAS associations with the largest effects map to loci characterized by strong recent selection, both geographically restricted positive selection (e.g., OCA2: Sulem et al. 2007) and global balancing selection (e.g., the ABO blood group locus: Stajich and Hahn 2005; Amundadottir et al. 2009).”
Liu, X., Li, C., Mou, C., Dong, Y., & Tu, Y.-C. (2020) · Genome Medicine · doi:10.1186/s13073-020-00803-9 · Cited by 652
“…MVP [27], PrimateAI [28], REVEL [29], SIFT4G [30]), one score for loss of function prediction (ALoFT [31]), and three conservation scores (phyloP17-way_primate [32], phastCons17way_primate [33], bStatistic [34]), making the total number of prediction scores to 46 (Additional file 1: Table S1).”
BackgroundGhisletti, S., Barozzi, I., Mietton, F., Polletti, S., De Santa, F., Venturini, E., Gregory, L., Lonie, L., Chew, A., Wei, C.-L., et al. (2010) · Immunity · doi:10.1016/j.immuni.2010.02.008 · Cited by 666
Dysfunction of lipid sensor GPR120 leads to obesity in both mouse and human
Ichimura, A., Hirasawa, A., Poulain‐Godefroy, O., Bonnefond, A., Hara, T., Yengo, L., Kimura, I., Leloire, A., Liu, N., Iida, K., et al. (2012) · Nature · doi:10.1038/nature10798 · Cited by 662
“Phylogenetic conservation of part of GPR120 containing each non-synonymous variant was assessed using UCSC genome browser (Vertebrate Multiz Alignment & Conservation), based on a phylogenetic hidden Markov model, phastCons 42 .”
MethodApplications of next-generation sequencing to phylogeography and phylogenetics
McCormack, J. E., Hird, S. M., Zellmer, A. J., Carstens, B. C., & Brumfield, R. T. (2011) · Molecular Phylogenetics and Evolution · doi:10.1016/j.ympev.2011.12.007 · Cited by 666
“, 2011) to invertebrates and yeast (Siepel et al., 2005) suggest that conserved probe sets for target enrichment may be applicable across a broad swath of the tree of life.”
BackgroundAn abundance of rare functional variants in 202 drug target genes sequenced in 14,002 people
Nelson, M. R., Wegmann, D., Ehm, M. G., Kessner, D., St. Jean, P., Verzilli, C., Shen, J., Tang, Z., Bacanu, S.-A., Fraser, D., et al. (2012) · Science · doi:10.1126/science.1217876 · Cited by 647
Rentzsch, P., Schubach, M., Shendure, J., & Kircher, M. (2021) · Genome Medicine · doi:10.1186/s13073-021-00835-9 · Cited by 640
Discovery of functional elements in 12 Drosophila genomes using evolutionary signatures
Stark, A., Lin, M. F., Kheradpour, P., Pedersen, J. S., Parts, L., Carlson, J. W., Crosby, M. A., Rasmussen, M. D., Roy, S., Deoras, A. N., et al. (2007) · Nature · doi:10.1038/nature06340 · Cited by 640
Self-citationGenome sequencing highlights the dynamic early history of dogs
Freedman, A. H., Gronau, I., Schweizer, R. M., Ortega-Del Vecchyo, D., Han, E., Silva, P. M., Galaverni, M., Fan, Z., Marx, P., Lorente-Galdos, B., et al. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004016 · Cited by 624
“In addition, we defined conserved non-coding elements (CNEs) on the basis of phastCons scores [37] (Text S7).”
MethodSelf-citationThe spotted gar genome illuminates vertebrate evolution and facilitates human-teleost comparisons
Braasch, I., Gehrke, A. R., Smith, J. J., Kawasaki, K., Manousaki, T., Pasquier, J., Amores, A., Desvignes, T., Batzel, P., Catchen, J., et al. (2016) · Nature Genetics · doi:10.1038/ng.3526 · Cited by 624
Metagenomics to Paleogenomics: Large-Scale Sequencing of Mammoth DNA
Poinar, H. N., Schwarz, C., Qi, J., Shapiro, B., MacPhee, R. D. E., Buigues, B., Tikhonov, A., Huson, D. H., Tomsho, L. P., Auch, A. F., et al. (2005) · Science · doi:10.1126/science.1123360 · Cited by 638
Self-citationGlobal mapping of translation initiation sites in mammalian cells at single-nucleotide resolution
Lee, S., Liu, B., Lee, S., Huang, S., Shen, B., & Qian, S. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1207846109 · Cited by 610
“Comparative genomics reveals that the coding regions often are evolutionarily conserved elements (33).”
BackgroundGenomic views of distant-acting enhancers
Visel, A., Rubin, E. M., & Pennacchio, L. A. (2009) · Nature · doi:10.1038/nature08451 · Cited by 610
“However, some observations have challenged such a generalized correlation between sequence conservation and enhancer activity: (1) experimental analysis of individual loci suggested that a large proportion of enhancers cannot be detected by comparative genomics 56, (2) a surprisingly large fraction of sequences in the…”
BackgroundBarrett, L. W., Fletcher, S., & Wilton, S. D. (2012) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-012-0990-9 · Cited by 641
“Despite this, regions of high conservation are also prevalent, with 30UTRs containing some of the most conserved elements within the mammalian genome [161].”
BackgroundA Network of Noncoding Regulatory RNAs Acts in the Mammalian Brain
Kleaveland, B., Shi, C. Y., Stefano, J., & Bartel, D. P. (2018) · Cell · doi:10.1016/j.cell.2018.05.022 · Cited by 610
A multi-omic atlas of the human frontal cortex for aging and Alzheimer’s disease research
De Jager, P. L., Ma, Y., McCabe, C., Xu, J., Vardarajan, B. N., Felsky, D., Klein, H.-U., White, C. C., Peters, M. A., Lodgson, B., et al. (2018) · Scientific Data · doi:10.1038/sdata.2018.142 · Cited by 598
Metadata
- Authors
- Siepel, A., Bejerano, G., Pedersen, J. S., Hinrichs, A. S., Hou, M., Rosenbloom, K., Clawson, H., Spieth, J., Hillier, L. W., Richards, S., Weinstock, G. M., Wilson, R. K., Gibbs, R. A., Kent, W. J., Miller, W., & Haussler, D.
- Affiliations
- University of California, Santa Cruz (US)
- ORCID
- Venue
- Genome Research
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2005-07-15
- Volume
- 15
- Issue
- 8
- Pages
- 1034-1050
- ISSN
- 1088-9051 (ISSN-L)
- PMC
- PMC1182216
- OpenAlex
- W7099666281
- Cited by
- 3,971
- References
- 96
- Citations by year
- 2026: 176 · 2025: 182 · 2024: 220 · 2023: 183 · 2022: 233 · 2021: 261 · 2020: 217 · 2019: 219 · 2018: 225 · 2017: 160 · 2016: 195 · 2015: 186 · 2014: 190 · 2013: 191 · 2012: 196
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genome Research (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- National Human Genome Research Institute (IP41HG02371, P41HG002371, R01HG002238)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Chromosomal and Genetic Variations
- Keywords
- conserved elements, ultraconserved elements, phastCons, multiple sequence alignment, non-coding DNA, vertebrate genomes, insect genomes, Caenorhabditis, Saccharomyces, Drosophila, Anopheles gambiae, gene deserts, 3' untranslated region, RNA secondary structure
- MeSH terms
- Animals, Base Sequence, Humans, Insecta, Molecular Sequence Data, Saccharomyces, Vertebrates, Yeasts, Genome, Conserved Sequence, Caenorhabditis elegans, Evolution, Molecular, Base Pairing, 3' Untranslated Regions, DNA, Intergenic
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-11-02, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-11-02 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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