The DOI matches its Crossref record; 77 of the 77 references it cites were found in a registry or an index; none of the 34 sources its claims cite is checked for support yet.
Analysis of 13 cell types reveals evidence for the expression of numerous novel primate- and tissue-specific microRNAs
Open accessAbstract
Significance: MicroRNAs (miRNAs) are small ∼22-nt RNAs that are important regulators of posttranscriptional gene expression. Since their initial discovery, they have been shown to be involved in many cellular processes, and their misexpression is associated with disease etiology. Currently, nearly 2,800 human miRNAs are annotated in public repositories. A key question in miRNA research is how many miRNAs are harbored by the human genome. To answer this question, we examined 1,323 short RNA sequence samples and identified 3,707 novel miRNAs, many of which are human-specific and tissue-specific. Our findings suggest that the human genome expresses a greater number of miRNAs than has previously been appreciated and that many more miRNA molecules may play key roles in disease etiology.
Overview
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Written from the paper’s full text.
TL;DR
Analyzing 1,323 short RNA-seq samples from 13 human cell types, this study identifies 3,707 novel mature miRNAs from 3,494 precursors at FDR ≤ 0.05, many of which are tissue-specific and primate-specific. The authors argue that public repositories substantially underrepresent the human miRNA repertoire.
Key findings
- From >23 billion sequenced reads, ~8.2 billion mapped unambiguously; 3,707 novel mature miRNAs were identified, and 91.5% (3,392 of 3,707) were discovered independently in at least 10 samples.
- Ago CLIP-seq supported 1,657 of 3,707 novel miRNAs (44.7%), compared with 1,517 of 2,772 miRBase release 20 miRNAs (54.7%).
- Novel miRNAs showed strong tissue dependence: low intertissue Jaccard similarity, PCA clustering by tissue, and stem-loop RT-PCR confirmation of 20 novel miRNAs in 12 cell lines representing 5 tissues.
- Conservation analysis found 56.7% of novel miRNAs human-specific and 94.4% primate lineage-specific; 2,140 (58.1%) precursor/mature combinations were human-specific, 476 (12.8%) shared across Hominidae, 109 (2.9%) present in mouse, and none in Drosophila or worm.
Methods
- Analyzed 1,323 short RNA-seq samples (100 in-house, 1,223 public) from 13 human cell types; reads were mapped to hg19 with SHRiMP2, processed per sample with miRDeep2, and filtered to mature miRNAs with FDR ≤ 0.05 after removing known miRNAs, mirtrons, tRNAs, snRNAs, and rRNAs.
- Used 43 Ago CLIP-seq samples (10 in-house, 33 public) to assess Argonaute loading, requiring complete coincidence with a CLIP-seq site, observation in at least one sample, and support by five or more reads.
- Validated selected novel miRNAs by stem-loop RT-PCR in 12 cell lines, assessed DICER dependence in MCF7 knockdown data, performed GLSEARCH conservation analysis, seed-based clustering, and RNA22 target prediction.
Limitations
- The paper states that the 43 Ago CLIP-seq samples represent only 3 of the 13 tissue types used for discovery, so not all novel or miRBase miRNAs are expected to be observed; lower Ago support for novel miRNAs is expected given their higher tissue specificity.
- The paper states that the study focused only on canonical Dicer-dependent miRNAs, while bona fide miRNAs can arise through other mechanisms, suggesting an even larger miRNA-ome.
- The paper states that RNA22 target predictions require additional experimental validation; only 20 novel miRNAs were experimentally tested by stem-loop RT-PCR.
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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
“Using stringent thresholding criteria, we identified 3,707 statistically significant novel mature miRNAs at a false discovery rate of ≤0.05 arising from 3,494 novel precursors; 91.5% of these novel miRNAs were identified independently in 10 or more of the processed samples.”
§ Analysis of 13 cell types reveals evidence for the expression of numerous novel primate-and tissue-specific microRNAs > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA 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
“Examination of the sequence conservation across vertebrate and invertebrate organisms showed 56.7% of the newly discovered miRNAs to be human-specific whereas the majority (94.4%) are primate lineage-specific.”
§ Analysis of 13 cell types reveals evidence for the expression of numerous novel primate-and tissue-specific microRNAs > Abstract
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“Our analysis showed that 709 of the miRNAs in release 20 of miRBase and 278 of our novel miRNAs were endogenously expressed in MCF7 cells.”
§ Analysis of 13 cell types reveals evidence for the expression of numerous novel primate-and tissue-specific microRNAs > Additional Experimental Support of Novel miRNAs by a Dicer
What the sources say
- Not matchedcites [39]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
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In the paper
“we found that only 10% of the precursor/mature miRNA combinations from miRBase were human-specific”
§ Analysis of 13 cell types reveals evidence for the expression of numerous novel primate-and tissue-specific microRNAs > Some of the Novel miRNAs Are Antisense to Known miRNAs or to
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In the paper
“Generally, we found their average expression level to be somewhat lower than that of miRBase miRNAs”
§ Analysis of 13 cell types reveals evidence for the expression of numerous novel primate-and tissue-specific microRNAs > Discussion
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In the paper
“the novel miRNAs can accurately cluster lymphoblastoid cell lines (LCLs), breast, platelets, B cells, skin, and brain tissue samples.”
§ Analysis of 13 cell types reveals evidence for the expression of numerous novel primate-and tissue-specific microRNAs > YES YES
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA 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
“Using stringent thresholding criteria, we identified 3,707 statistically significant novel mature miRNAs at a false discovery rate of ≤0.05 arising from 3,494 novel precursors; 91.5% of these novel miRNAs were identified independently in 10 or more of the processed samples.”
§ Analysis of 13 cell types reveals evidence for the expression of numerous novel primate-and tissue-specific microRNAs > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA 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
“We found that 2,140 (58.1%) precursor/mature miRNA combinations were specific to humans”
§ Analysis of 13 cell types reveals evidence for the expression of numerous novel primate-and tissue-specific microRNAs > Some of the Novel miRNAs Are Antisense to Known miRNAs or to
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“of our 3,707 novel miRNAs, only 292 are in common with the miRNAs discovered by another recently reported effort (33) that also used miRDeep2.”
§ Analysis of 13 cell types reveals evidence for the expression of numerous novel primate-and tissue-specific microRNAs > Discussion
What the sources say
- Not matchedcites [33]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
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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
“the novel miRNAs that we discovered in a given tissue had limited presence outside that tissue, indicating their strong tissuedependent nature.”
§ Analysis of 13 cell types reveals evidence for the expression of numerous novel primate-and tissue-specific microRNAs > YES YES
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- It may state two separate claims as one. 26
- Probably not a substantial claim. 14
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 results remained largely unchanged, with the large majority of the newly identified sequences continuing to be primate-specific”
§ Analysis of 13 cell types reveals evidence for the expression of numerous novel primate-and tissue-specific microRNAs > Some of the Novel miRNAs Are Antisense to Known miRNAs or to
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“After siRNA knockdown of DICER1, the miRBase miRNAs showed a median decrease in expression of ∼2×, and our novel miRNAs showed a median decrease in expression of ∼1.6×”
§ Analysis of 13 cell types reveals evidence for the expression of numerous novel primate-and tissue-specific microRNAs > Additional Experimental Support of Novel miRNAs by a Dicer
What the sources say
- Not matchedcites [39]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
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In the paper
“We identified 31 such clusters, 21 of which were comprised exclusively of novel miRNAs”
§ Analysis of 13 cell types reveals evidence for the expression of numerous novel primate-and tissue-specific microRNAs > Several of the Newly Discovered miRNAs Are Arranged in Genomic
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In the paper
“we computationally predicted their mRNA targets using RNA22 (30,58) to generate predictions of the mRNA targets for each of the 3,707 newly discovered miRNAs.”
§ Analysis of 13 cell types reveals evidence for the expression of numerous novel primate-and tissue-specific microRNAs > Some of the Novel miRNAs Are Antisense to Known miRNAs or to
What the sources say
- Not matchedcites [30]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [58]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
- The authors state this as an assumption: The novel miRNAs will affect many pathways and exert their effects on a wide range of targets.
- Not matched
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 second group of novel miRNAs was ubiquitously expressed and present in all of the examined cell lines.”
§ Analysis of 13 cell types reveals evidence for the expression of numerous novel primate-and tissue-specific microRNAs > Additional Experimental Support of Novel miRNAs by a Dicer
Strength:plain· not yet calibratedn = 12Tests✓ 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 first group of tested miRNAs indeed exhibited tissue-specific expression patterns: Each of the 12 miRNAs was present in one or more of the tested cell lines.”
§ Analysis of 13 cell types reveals evidence for the expression of numerous novel primate-and tissue-specific microRNAs > Additional Experimental Support of Novel miRNAs by a Dicer
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In the paper
“The 873 common seeds captured 2,146 of our novel miRNAs; the remaining 1,561 novel miRNAs had 888 distinct seed sequences not present in an annotated miRBase miRNA”
§ Analysis of 13 cell types reveals evidence for the expression of numerous novel primate-and tissue-specific microRNAs > Many Novel miRNAs Are Seed-Paralogues of Known miRBase miRNAs.
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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
“Among the newly identified miRNAs are many novel miRNA clusters, new members of known miRNA clusters, previously unreported products from uncharacterized arms of miRNA precursors, and previously unrecognized paralogues of functionally important miRNA families (e.g., miR-15/107).”
§ Analysis of 13 cell types reveals evidence for the expression of numerous novel primate-and tissue-specific microRNAs > 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
“identified 13 such instances, 9 of which comprise only novel miRNA pairs.”
§ Analysis of 13 cell types reveals evidence for the expression of numerous novel primate-and tissue-specific microRNAs > Some of the Novel miRNAs Are Antisense to Known miRNAs or to
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
“Analysis of these novel miRNAs revealed tissue-specific dependencies and a commensurate low Jaccard similarity index in intertissue comparisons.”
§ Analysis of 13 cell types reveals evidence for the expression of numerous novel primate-and tissue-specific microRNAs > 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
“109 (2.9%) of them were present in mouse whereas none were present in the Drosophila or worm genomes.”
§ Analysis of 13 cell types reveals evidence for the expression of numerous novel primate-and tissue-specific microRNAs > Some of the Novel miRNAs Are Antisense to Known miRNAs or to
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“not surprisingly then, 56.7% of our newly discovered miRNAs are human-specific whereas 94.4% are primate-specific (Table 2).”
§ Analysis of 13 cell types reveals evidence for the expression of numerous novel primate-and tissue-specific microRNAs > Discussion
What the sources say
- Not matchedcites Table 2
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
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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
“Analysis of our collection of identified miRNAs revealed that 10 of the novel miRNAs that we discovered were included in release 21 of miRBase.”
§ Analysis of 13 cell types reveals evidence for the expression of numerous novel primate-and tissue-specific microRNAs > RNA Sequencing.
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
“Taken together, these results suggest that the identified novel miRNAs display patterns of tissue specificity and can distinguish among tissue types.”
§ Analysis of 13 cell types reveals evidence for the expression of numerous novel primate-and tissue-specific microRNAs > YES YES
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- The authors state this as an assumption: miRNAs exhibit tissue-specific behavior similar to protein-coding genes.
In the paper
“We further postprocessed the identified mature miRNAs and precursors to remove any predicted mature miRNA that (i) is already represented in miRBase release 20 or in the mirtron catalog (28) and/or (ii) colocalized with snRNAs, tRNAs, and rRNAs even though such loci have been previously linked with miRNA production”
§ Analysis of 13 cell types reveals evidence for the expression of numerous novel primate-and tissue-specific microRNAs > Results
What the sources say
- Not matchedcites [28]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
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In the paper
“There are two reasons for this small overlap: first, the 1,323 samples that we analyzed and the 94 samples analyzed in ref. 33 have only one dataset in common (NIH GEO accession no.GSE15229; 30 samples).And second, our novel miRNAs (as evidenced by Fig. 3A) and those discovered in ref. 33 are tissue-specific.”
§ Analysis of 13 cell types reveals evidence for the expression of numerous novel primate-and tissue-specific microRNAs > Discussion
What the sources say
- Not matchedcites [33]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
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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
“the existence of novel miRNAs that are primate-and tissue-specific indicates the existence of molecular interactions that cannot be recapitulated by mouse models and, thus, has potential implications for both disease and research endeavors.”
§ Analysis of 13 cell types reveals evidence for the expression of numerous novel primate-and tissue-specific microRNAs > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: There is no reason to think that there will not be lineage-specific adaptive evolution in regulatory sequences and regulatory molecules.
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 results suggest that about half of our newly identified miRNAs are loaded onto the Ago-silencing complex and thus are imputed to be posttranscriptionally functional.”
- Also stated in: § Discussion · hedged
“many of the novel miRNAs are loaded onto the Ago-silencing complex, which suggests that they are biologically active.”
§ Analysis of 13 cell types reveals evidence for the expression of numerous novel primate-and tissue-specific microRNAs > YES YES
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Also stated in: § Discussion · hedged
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In the paper
“we normalized the expression level of each miRNA as previously described (44,45) and separately for each sample.From each analyzed sample, we kept only very abundant novel miRNAs [i.e., novel miRNAs with expression levels ≥1/100 the expression of the endogenous small nucleolar RNA (snoRNA) SNORD44 (44, 45)]”
§ Analysis of 13 cell types reveals evidence for the expression of numerous novel primate-and tissue-specific microRNAs > YES YES
What the sources say
- Not matchedcites [44]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [45]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
- Not matched
In the paper
“This result indicates that those of our newly discovered miRNAs that are endogenous to MCF7 cells are DICER-dependent and follow the canonical biogenesis pathway.”
§ Analysis of 13 cell types reveals evidence for the expression of numerous novel primate-and tissue-specific microRNAs > Additional Experimental Support of Novel miRNAs by a Dicer
What the sources say
- Not matchedcites [39]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
“Each mature miRNA candidate had to completely coincide with an Ago CLIP-seq site, be observed in at least 1 of the 43 CLIP-seq samples, and be supported by five or more unambiguously mapped CLIP-seq reads.”
§ Analysis of 13 cell types reveals evidence for the expression of numerous novel primate-and tissue-specific microRNAs > Identification of Significantly Expressed Sample-Dependent Novel miRNAs.
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
“Additionally, to eliminate noisy lowly expressed miRs, we kept a discovered miRNA only if it had an associated FDR ≤ 0.05.”
§ Analysis of 13 cell types reveals evidence for the expression of numerous novel primate-and tissue-specific microRNAs > Identification of Significantly Expressed Sample-Dependent Novel miRNAs.
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In the paper
“One important property of RNA22 is that it is not confined on the 3′ UTR alone but can generate predictions across the entire length of an mRNA.”
§ Analysis of 13 cell types reveals evidence for the expression of numerous novel primate-and tissue-specific microRNAs > Discussion
What the sources say
- Not matchedcites [30]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [58]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
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.
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In the paper
“We opted to use RNA22 (https://cm.jefferson.edu/rna22v2/) because of its demonstrated ability to correctly predict targets in amino acid coding regions and in 5′ UTRs, as well as targets that do not contain contiguous Watson-Crick base pairs in their seed region.”
§ Analysis of 13 cell types reveals evidence for the expression of numerous novel primate-and tissue-specific microRNAs > Some of the Novel miRNAs Are Antisense to Known miRNAs or to
What the sources say
- Not matchedcites [30]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [58]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Not matched
In the paper
“For example, the members of the miR-29 family share the same seed sequence but display differences in the predicted targetomes: miR-29b localizes predominantly in the nucleus whereas miR-29a and miR-29c do not (69).”
§ Analysis of 13 cell types reveals evidence for the expression of numerous novel primate-and tissue-specific microRNAs > Discussion
What the sources say
- Not matchedcites [69]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
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.
- Not matched
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In the paper
“This release of miRBase comprises 1,871 precursor sequences and 2,772 mature miRNAs.”
§ Analysis of 13 cell types reveals evidence for the expression of numerous novel primate-and tissue-specific microRNAs > RNA Sequencing.
What the sources say
- Not matchedcites [31]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [32]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
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.
- 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
“During these searches, we required that (i) at least 85% of the miRNA precursor positions be identically conserved in the searched genome and (ii) at least 85% of the human mature miRNA positions be identically present in the identified orthologous precursor, including an identically present seed.”
§ Analysis of 13 cell types reveals evidence for the expression of numerous novel primate-and tissue-specific microRNAs > Genome Conservation of Hairpin and Mature miRNAs.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
In the paper
“Therefore, enforcing an organism-conservation requirement during miRNA searches is bound to limit the number of potential miRNAs that can be discovered, leaving organism-and lineage-specific miRNAs undiscovered (53)(54)(55)(56).”
§ Analysis of 13 cell types reveals evidence for the expression of numerous novel primate-and tissue-specific microRNAs > Discussion
What the sources say
- Not matchedcites (53)(54)(55)(56)
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
“we imposed two requirements: (i) At least 85% of the miRNA precursor positions should be identically present in the genome being searched, and (ii) at least 85% of the human mature miRNA sequence should be identically present in the identified orthologous precursor, including an identically present seed.”
§ Analysis of 13 cell types reveals evidence for the expression of numerous novel primate-and tissue-specific microRNAs > Some of the Novel miRNAs Are Antisense to Known miRNAs or to
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It 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
“Indeed, it is reasonable to expect that at least some of these novel primate-specific miRNAs participate in unexplored aspects of regulatory processes that cannot be captured by the currently available mouse disease models.”
§ Analysis of 13 cell types reveals evidence for the expression of numerous novel primate-and tissue-specific microRNAs > Discussion
Tests✓ Asserted: passes✗ Checkable: fails✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may be too vague to check against evidence.
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
“As a negative control, a primer to a scrambled miRNA sequence was designed.U6 RT-PCR was performed on all samples to control for the RNA concentrations.”
§ Analysis of 13 cell types reveals evidence for the expression of numerous novel primate-and tissue-specific microRNAs > Experimental Amplification of Novel miRNAs.
Strength:plain· not yet calibratedn = 12Tests✓ 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
“These steps allow us to compensate for differences in sequence depth among the various samples and to select only miRNAs with statistically significant abundance in the sample being considered each time.”
§ Analysis of 13 cell types reveals evidence for the expression of numerous novel primate-and tissue-specific microRNAs > Identification of Significantly Expressed Sample-Dependent Novel miRNAs.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“Based on the results presented here and taking into account previous studies (28,33), we conclude that the miRNAs currently listed in the public repositories represent only a small fraction of the total human miRNA repertoire and that many more human miRNAs await discovery.”
§ Analysis of 13 cell types reveals evidence for the expression of numerous novel primate-and tissue-specific microRNAs > Discussion
What the sources say
- Not matchedcites [28]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [33]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Not matched
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
“The sheer magnitude of the identified miRNAs and the very high number of predicted targets for each such miRNA make the experimental validation of the targetome by a single laboratory an intractable proposition.”
§ Analysis of 13 cell types reveals evidence for the expression of numerous novel primate-and tissue-specific microRNAs > Discussion
Tests✓ Asserted: passes✗ Checkable: fails✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may be too vague to check against evidence.
- Rests on an assumption: The remainder of the miRNA sequence can assist in defining the eventual targetome.
The authors state this as an assumption.
The novel miRNAs will affect many pathways and exert their effects on a wide range of targets.
“It is reasonable to assume that these novel miRNAs will affect many pathways and exert their effects on a wide range of targets.”
The authors state this as an assumption.
miRNAs exhibit tissue-specific behavior similar to protein-coding genes.
“Just as protein-coding genes display tissue-specific patterns of expression, it is reasonable to assume that miRNAs would exhibit a similar behavior.”
The paper relies on this without support.
Many more miRNAs are present and can be identified through analysis of additional samples representing more diverse tissue types.
“We reasoned that many more miRNAs are present and can be identified through the analysis of additional samples representing more diverse tissue types.”
The paper relies on this without support.
There is no reason to think that there will not be lineage-specific adaptive evolution in regulatory sequences and regulatory molecules.
“Indeed, there is no reason to think that there will not be lineage-specific adaptive evolution in regulatory sequences and regulatory molecules.”
The paper relies on this without support.
MiRNAs loaded onto the Argonaute complex are capable of interacting with target RNAs.
“MiRNAs exert their function through their association with the Argonaute complex, and, thus, those miRNAs loaded onto Ago are expected to be capable of interacting with target RNAs.”
The paper relies on this without support.
The remainder of the miRNA sequence can assist in defining the eventual targetome.
“Nonetheless, the remainder of the miRNA sequence can also assist in defining the eventual targetome.”
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 doesn’t support the claim as written.
In the citing paper
“Too many “novel miRNAs” lack clear miRNA features and have only served to further complicate the miRNA field [17, 35, 36].”
From A curated human cellular microRNAome based on 196 primary cell types (2022) · cites this paper as [35]
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“The remaining miRBase microRNAs had modest conservation and were similarly distributed to both the putative novel microRNAs reported here and the 3707 novel microRNAs reported as TJU microRNAs (Fig. 3B; Londin et al. 2015).”
From Toward the human cellular microRNAome (2017) · cites this paper as Londin et al. 2015
The cited source says what the claim attributes to it.
In the citing paper
“The PhyloP conservation data (Fig. 3B) show that, beyond the most ideal microRNAs identified in miRGeneDB, there is a lack of genetic conservation, with overlap in a large segment of miRBase microRNAs and the novel microRNAs reported here and in a prior large study (Londin et al. 2015).”
From Toward the human cellular microRNAome (2017) · cites this paper as Londin et al. 2015
The cited source says what the claim attributes to it.
In the citing paper
“In comparison to the 3707 novel TJU microRNAs (Londin et al. 2015), only 257 (52%) were shared between both data sets.”
From Toward the human cellular microRNAome (2017) · cites this paper as Londin et al. 2015
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.
Drosophila conservation percentage is miscalculated
MinorTable 2 reports six of 3,707 novel combinations as 0.25%; that fraction is about 0.16%.
Reported 0.25 · recomputed 0.161856
“| Drosophila | 6 (0.25%) | 5 (0.3%) | 4 (0.14%) |”
Figure 5 assigns different meanings to its rows
MinorThe caption says each row represents one miRNA, then says each row represents a cell line.
“Stem-loop RT-PCR experiments for 20 newly discovered miRNAs (one miRNA per row).”
“Each row represents a specific cell line.”
Claim of no invertebrate conservation conflicts with Table 2
MinorThe prose says none of the novel combinations were present in Drosophila or worm, but Table 2 lists six and two, respectively.
“none were present in the Drosophila or worm genomes.”
“| Drosophila | 6 (0.25%) | 5 (0.3%) | 4 (0.14%) | | Worm | 2 (0.05%) | 1 (0.06%) | 1 (0.03%) |”
The number of analyzed short RNA samples changes to 1,232
MinorThe paper consistently gives 1,323 as the number of analyzed short RNA-seq samples, but the Ago CLIP-seq discussion calls the analyzed collection 1,232 samples.
“these cells were not represented among the 1,232 short RNA sequence samples that were analyzed.”
“we used it to analyze our collection by processing each of the 1,323 samples separately”
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The role of microRNAs in the development and progression of chemical-associated cancers
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A high-resolution map of the human small non-coding transcriptome
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Post-transcriptional Regulation of BRCA2 through Interactions with miR-19a and miR-19b
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Metadata
- Authors
- Londin, E., Loher, P., Telonis, A. G., Quann, K., Clark, P., Jing, Y., Hatzimichael, E., Kirino, Y., Honda, S., Lally, M., Ramratnam, B., Comstock, C. E. S., Knudsen, K. E., Gomella, L., Spaeth, G. L., Hark, L., Katz, L. J., Witkiewicz, A., Rostami, A., Jimenez, S. A., Hollingsworth, M. A., Yeh, J. J., Shaw, C. A., McKenzie, S. E., Bray, P., Nelson, P. T., Zupo, S., Van Roosbroeck, K., Keating, M. J., Calin, G. A., Yeo, C., Jimbo, M., Cozzitorto, J., Brody, J. R., Delgrosso, K., Mattick, J. S., Fortina, P., & Rigoutsos, I.
- Affiliations
- Thomas Jefferson University (US)
- Computational Medicine Center, Sidney Kimmel Medical School at Thomas Jefferson University, Philadelphia, PA 19107;
- Brown University (US)
- American Association For Cancer Research (US)
- Wills Eye Hospital (US)
- The University of Texas Southwestern Medical Center (US)
- Jefferson Institute of Molecular Medicine and The Scleroderma Center, Sidney Kimmel Medical School at Thomas Jefferson University, Philadelphia, PA 19107;
- University of Nebraska Medical Center (US)
- University of North Carolina at Chapel Hill (US)
- Baylor College of Medicine (US)
- University of Kentucky (US)
- Ospedale Policlinico San Martino (IT)
- Department of Experimental Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX 77030;
- The University of Texas MD Anderson Cancer Center (US)
- Leukemia Department, University of Texas MD Anderson Cancer Center, Houston, TX 77030;
- Garvan Institute of Medical Research (AU)
- ORCID
- Londin, Eric
- Loher, Phillipe
- Telonis, Aristeidis G.
- Quann, Kevin
- Clark, Peter
- Hatzimichael, Eleftheria
- Kirino, Yohei
- Lally, Michelle
- Comstock, Clay E. S.
- Knudsen, Karen E.
- Gomella, Leonard
- Spaeth, George L.
- Hark, Lisa
- Katz, L. Jay
- Witkiewicz, Agnieszka
- Rostami, Abdolmohamad
- Hollingsworth, Michael A.
- Yeh, Jen Jen
- Shaw, Chad A.
- McKenzie, Steven E.
- Bray, Paul
- Nelson, Peter T.
- Zupo, Simona
- Keating, Michael J.
- Yeo, Charles
- Jimbo, Masaya
- Brody, Jonathan R.
- Mattick, John S.
- Fortina, Paolo
- Rigoutsos, Isidore
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2015-02-23
- Volume
- 112
- Issue
- 10
- Pages
- E1106-15
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4364231
- OpenAlex
- W2022326327
- Cited by
- 404
- References
- 74
- Citations by year
- 2026: 6 · 2025: 16 · 2024: 10 · 2023: 22 · 2022: 22 · 2021: 22 · 2020: 27 · 2019: 51 · 2018: 49 · 2017: 76 · 2016: 75 · 2015: 28
- FWCI
- 24.06
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion, other-oa)
- UKnowledge (University of Kentucky) (submittedVersion)
- Funders
- U.S. Department of Defense
- W. M. Keck Foundation
- RGK Foundation
- Hirshberg Foundation for Pancreatic Cancer Research
- CLL Global Research Foundation
- Thomas Jefferson University (P30CA56036)
- Deutsches Krebsforschungszentrum
- Laura and John Arnold Foundation
- Weizmann Institute of Science
- National Institutes of Health (#AG028383)
- University of Texas MD Anderson Cancer Center
- Center for AIDS Research, University of Washington
- National Institute on Aging (P30AG028383, R01AG042419)
- National Heart, Lung, and Blood Institute (R01HL116713, R01HL102482)
- National Cancer Institute (R01CA140424, P50CA127297, R01CA099996, P30CA016672, P30CA056036, P30CA036727)
- National Institute of General Medical Sciences (R01GM106047)
- National Institute of Allergy and Infectious Diseases (U19AI056363, P30AI042853)
- National Institute of Neurological Disorders and Stroke (R21NS085830)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR019616)
- National Institute on Minority Health and Health Disparities (R01MD007880)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Molecular Biology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Chromosomal and Genetic Variations
- Keywords
- microRNA, novel miRNA discovery, microRNA precursors, tissue-specific gene expression, miRNA clusters, RNA interference, human cell lines
- MeSH terms
- Animals, Base Sequence, Primates, Sequence Alignment, Genome, MicroRNAs, Ribonuclease III, Gene Knockdown Techniques
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 2026-11-06, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-11-06 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
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.
What counts as a claim ›How we measure confidence ›How we check this ›
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