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Cited by 611Genomics and Phylogenetic StudiesGenome Rearrangement AlgorithmsChromosomal and Genetic Variations

Progressive Cactus is a multiple-genome aligner for the thousand-genome era

Open access
Armstrong, Joel, Hickey, Glenn, Diekhans, Mark, Fiddes, Ian T., Novak, Adam M., Deran, Alden, Fang, Qi, Xie, Duo +13 more·2020·Nature
DOI 10.1038/s41586-020-2871-yPMC PMC7673649
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Abstract

New genome assemblies have been arriving at a rapidly increasing pace, thanks to decreases in sequencing costs and improvements in third-generation sequencing technologies 1–3 . For example, the number of vertebrate genome assemblies currently in the NCBI (National Center for Biotechnology Information) database 4 increased by more than 50% to 1,485 assemblies in the year from July 2018 to July 2019. In addition to this influx of assemblies from different species, new human de novo assemblies 5 are being produced, which enable the analysis of not only small polymorphisms, but also complex, large-scale structural differences between human individuals and haplotypes. This coming era and its unprecedented amount of data offer the opportunity to uncover many insights into genome evolution but also present challenges in how to adapt current analysis methods to meet the increased scale. Cactus 6 , a reference-free multiple genome alignment program, has been shown to be highly accurate, but the existing implementation scales poorly with increasing numbers of genomes, and struggles in regions of highly duplicated sequences. Here we describe progressive extensions to Cactus to create Progressive Cactus, which enables the reference-free alignment of tens to thousands of large vertebrate genomes while maintaining high alignment quality. We describe results from an alignment of more than 600 amniote genomes, which is to our knowledge the largest multiple vertebrate genome alignment created so far.

AI snapshot

Written from the paper’s full text.

TL;DR

Progressive Cactus extends the reference-free Cactus aligner with a progressive strategy that scales linearly with genome number while retaining high accuracy and ancestral reconstruction. The authors demonstrate it on simulated data, guide-tree and assembly-quality tests, and a 605-genome amniote alignment spanning more than 1 trillion bases.

Key findings

  • Progressive Cactus achieved higher Alignathon accuracy than any participating aligner, with F1 scores of 0.989 for simulated primates and 0.795 for simulated mammals. In simulated catarrhine alignments, progressive mode reduced runtime by 15% for 10 species and 48% for 20 species versus a star-tree strategy.
  • Guide-tree choice had limited impact: across four alignments of 48 avian species on chromosome 1, an average of 98.5% of aligned pairs were identical between any two alignments, and pairwise species F1 scores between Jarvis- and Prum-based trees were at least 0.955.
  • The 600-way amniote alignment combined 242 Zoonomia mammals and 363 B10K avians, totaling 605 genomes and 1.07 trillion bases, using 73,692 instance-hours and 2.1 million core-hours; the combined common ancestor size was 181 Mb. Median human coverage was 2.3 Gb from Euarchonta, 1.2 Gb from Laurasiatheria, and 1.0 Gb from Glires.
  • Ancestral reconstructions retained 86% of human coding bases in the placental ancestor and 95% of chicken coding bases in the avian ancestor. Best-hit filtering reduced human sequence mapping to two or more chimpanzee locations from 6.1% to 2.6% and reduced inferred paralogous alignments from 46% to 26%; Progressive Cactus covered 69.4% of chicken versus 64.9% for MULTIZ, and 79% of zebra finch versus 49.2% for MULTIZ.

Methods

  • Progressive Cactus uses an input guide tree to recursively split whole-genome alignment into subproblems, each comparing ingroup genomes plus outgroup genomes; subproblems use LASTZ local alignments, CAF and BAR algorithms, and ancestral assembly reconstruction, with results combined into HAL format.
  • Evaluations included Alignathon simulated primate and mammal datasets; twenty simulated 30-Mb catarrhine genomes under progressive versus star trees; 48 avian species reduced to chicken chromosome 1 under four guide trees; 11 boreoeutherian mammals with high- versus low-quality assemblies; and the 605-genome amniote alignment.
  • Main analyses compared runtime, precision/recall/F1 against truth sets, Jaccard similarity of aligned pairs, coverage statistics, micro-indel rates, RepeatMasker annotations, and transcript/gene mappings against BLAT, BLAST, LASTZ, and MULTIZ.

Limitations

  • Stated: ancestral reconstructions are hypothetical histories; ancestral base calls are generated during alignment and may differ from ideal post hoc calls, though `ancestorsML` can re-estimate them. Adding a genome to an existing alignment re-infers at most one ancestral sequence, so rare sequence in the new genome may not align properly to distant outgroups.
  • Stated: paralogy resolution forbids representing incomplete lineage sorting or horizontal transfer and cannot exactly order multiple duplication events along a single branch. Guide trees can affect alignments, though multiple outgroups reduce this effect, and poor assembly quality can still alter alignments.
  • Evident: the 600-way alignment is a composite of the Zoonomia and B10K alignments joined by a linker alignment using frog, coelacanth, and zebrafish outgroups, not a single monolithic run; it also required large computational resources (2.1 million core-hours).

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1038/s41586-020-2871-y

Cites

66 of 66 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

40 of 49 cited sources checked · 21 supported · 0 flagged · accuracy not yet measured

  • Findingown data

    Comparing induced pairwise human-dog alignments to direct pairwise alignments computed using the chains and nets pipeline, the same level of Jaccard similarity was found for both high- and low-quality assembly alignments.

    “Reinforcing this, comparing the induced pairwise alignments of human–dog to direct pairwise alignments computed using the established chains and nets pipeline30, we find the same level of Jaccard similarity for both the high- and low-quality assembly alignments (Supplementary Fig. 5).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [30] Kent, W. J., Baertsch, R., Hinrichs, A., Miller, W. & Haussler, D. Evolution’s cauldron: duplication, deletion, and rearrangement in the mouse and human genomes. Proc. Natl Acad. Sci. USA 100, 11484–11489 (2003). source
  • Premisecitation

    Comparative genomics analyses (species-tree inference, comparative annotation, selection detection) require genome alignments.

    “Comparative genomics analyses, including species-tree inference7,8, comparative annotation9,10, and selection detection11,12, require genome alignments.”
    Quote in the paperSubstantial claim5 of 6 sources checked
    • cites [7] Liu, L., Yu, L. & Edwards, S. V. A maximum pseudo-likelihood approach for estimating species trees under the coalescent model. BMC Evol. Biol. 10, 302 (2010). source

      The Methods section (page not available) describes estimating gene trees from multilocus sequences and resampling sites in aligned sequences, supporting the use of alignments for species-tree inference. But it says MP-EST constructs a species tree from rooted gene trees; it does not establish that genome alignments are required. This citation supports the species-tree portion of the sentence, not the separately cited annotation and selection examples. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
    • cites [8] Zhang, C., Rabiee, M., Sayyari, E. & Mirarab, S. ASTRAL-III: polynomial time species tree reconstruction from partially resolved gene trees. BMC Bioinformatics 19 (Suppl. 6), 153 (2018). source

      The Background (page unavailable) describes species-tree inference from gene trees drawn from different parts of the genome, and the Results discuss gene alignments. But the Methods define ASTRAL’s input as gene trees, not genome alignments, so the paper does not establish the claimed requirement for genome alignments. This citation is attached to species-tree inference, not comparative annotation or selection detection. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
    • cites [9] Fiddes, I. T. et al. Comparative annotation toolkit (CAT)-simultaneous clade and personal genome annotation. Genome Res. 28, 1029–1038 (2017). source
    • cites [10] König, S., Romoth, L. W., Gerischer, L. & Stanke, M. Simultaneous gene finding in multiple genomes. Bioinformatics 32, 3388–3395 (2016). source

      This citation is attached to comparative annotation, not species-tree inference or selection detection. The Abstract says AUGUSTUS cgp requires a genome alignment, supporting the claim for this method. But the Conclusion (section 4) describes protein or transcript alignment as another way to transfer annotations, so the paper does not establish that comparative annotation generally requires genome alignments. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • cites [11] Hubisz, M. J., Pollard, K. S. & Siepel, A. PHAST and RPHAST: phylogenetic analysis with space/time models. Brief. Bioinform. 12, 41–51 (2011). source
    • cites [12] Garber, M. et al. Identifying novel constrained elements by exploiting biased substitution patterns. Bioinformatics 25, i54–i62 (2009). source
  • Premisecitation

    The Alignathon simulated datasets have a known truth set, providing a way to compare Progressive Cactus against other genome aligners.

    “The Alignathon simulated datasets14 have been aligned with many competing genome aligners and have a known truth set, providing a way to compare Progressive Cactus against other genome aligners.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [14] Earl, D. et al. Alignathon: a competitive assessment of whole-genome alignment methods. Genome Res. 24, 2077–2089 (2014). source
  • Premisecitation

    Different genome aligners frequently give different results.

    “different aligners frequently give different results14”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [14] Earl, D. et al. Alignathon: a competitive assessment of whole-genome alignment methods. Genome Res. 24, 2077–2089 (2014). source
  • Findingcitation

    Progressive Cactus, combined with HAL toolkit, supports addition and removal of genomes from the alignment.

    “Progressive Cactus, combined with special functionality in the HAL toolkit27, therefore supports the addition and removal of genomes from the alignment”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [27] Hickey, G., Paten, B., Earl, D., Zerbino, D. & Haussler, D. HAL: a hierarchical format for storing and analyzing multiple genome alignments. Bioinformatics 29, 1341–1342 (2013). source

      Section 2.3 (HAL tools; page not specified) describes a Cactus-to-HAL converter, supporting the claimed connection between Cactus and the HAL toolkit. Neither that section nor the passages found by searching for genome addition and removal say that the toolkit supports adding or removing genomes from an existing alignment. (LLM, conf=0.78)

      Experimental — accuracy not yet measured
  • Classified as probably not a substantial claim. 27
  • May combine two claims. 38

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Progressive Cactus has been developed over several years and has already been successfully used as an integral component of high-profile comparative genomics projects.

    “Progressive Cactus has been developed over several years, and has already been successfully used as an integral component of high-profile comparative genomics projects16–20.”
    Quote in the paperNot a substantial claim5 of 5 sources checked
    • cites [16] Green, R. E. et al. Three crocodilian genomes reveal ancestral patterns of evolution among archosaurs. Science 346, 1254449 (2014). source

      The Materials and Methods section (“Genome alignments and ancestral genome reconstruction”; page unavailable) says progressive-cactus computed the 23-taxon whole-genome alignment, supporting its use as an integral component of this comparative genomics project. The paper does not establish that Progressive Cactus had been developed over several years; its References section cites a 2011 paper on Cactus, but gives no development timeline for Progressive Cactus. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
    • cites [17] Dobrynin, P. et al. Genomic legacy of the African cheetah, Acinonyx jubatus. Genome Biol. 16, 277 (2015). source

      The Results and Materials and methods (pages unavailable) report that Progressive Cactus was used to align the cheetah genome with other mammalian genomes, supporting its use in a comparative genomics project. This paper does not establish that the software was developed over several years or used in multiple projects. (LLM, conf=0.87)

      Experimental — accuracy not yet measured
    • cites [18] Gordon, D. et al. Long-read sequence assembly of the gorilla genome. Science 352, aae0344 (2016). source

      The Abstract and Comparative analyses section describe a gorilla-genome assembly and comparisons with human, but do not identify Progressive Cactus as a component. Searches for “Progressive Cactus” and Cactus genome alignment found no passage addressing its use in this project or its development over several years. Page numbers were not available in our copy. (LLM, conf=0.70)

      Experimental — accuracy not yet measured
    • cites [19] Lilue, J. et al. Sixteen diverse laboratory mouse reference genomes define strain-specific haplotypes and novel functional loci. Nat. Genet. 50, 1574–1583 (2018). source
    • cites [20] Kronenberg, Z. N. et al. High-resolution comparative analysis of great ape genomes. Science 360, eaar6343 (2018). source

      The Results (Comparative sequence analyses; page unavailable) describe a five-way great ape genome alignment, but do not identify Progressive Cactus as a component. Searches for “Progressive Cactus” and “Cactus alignments” found only a reference to an earlier Cactus paper, not evidence that this project used Progressive Cactus or that it had been developed over several years. (LLM, conf=0.76)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The number of vertebrate genome assemblies in the NCBI database increased by more than 50% to 1,485 assemblies in the year from July 2018 to July 2019.

    “the number of vertebrate genome assemblies currently in the NCBI (National Center for Biotechnology Information) database4 increased by more than 50% to 1,485 assemblies in the year from July 2018 to July 2019.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [4] Kitts, P. A. et al. Assembly: a resource for assembled genomes at NCBI. Nucleic Acids Res. 44 (D1), D73–D80 (2016). source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    New human de novo assemblies are being produced, enabling analysis of small polymorphisms and complex large-scale structural differences between human individuals and haplotypes.

    “new human de novo assemblies5 are being produced, which enable the analysis of not only small polymorphisms, but also complex, large-scale structural differences between human individuals and haplotypes.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [5] Jain, M. et al. Nanopore sequencing and assembly of a human genome with ultra-long reads. Nat. Biotechnol. 36, 338–345 (2018). source

  • May combine two claims.

    Premisecitation

    Cactus is a reference-free multiple genome alignment program that has been shown to be highly accurate.

    “Cactus6, a reference-free multiple genome alignment program, has been shown to be highly accurate”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [6] Paten, B. et al. Cactus: algorithms for genome multiple sequence alignment. Genome Res. 21, 1512–1528 (2011). source

  • May combine two claims.

    Findingcitation

    The amniote-wide alignment combines two smaller alignments: one for the Zoonomia project including 242 placental mammals representing most eutherian mammal families, and one for the Bird 10,000 genomes (B10K) project including 363 avians representing most bird families.

    “The amniote-wide alignment combines two smaller alignments: one created for the initial release of the Zoonomia project31, which includes 242 placental mammals representing most eutherian mammal families, and one for the Bird 10,000 genomes (B10K) project32, which includes 363 avians, also representing most bird families.”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [31] Zoonomia Consortium. A comparative genomics multitool for scientific discovery and conservation. Nature https://doi.org/10.1038/s41586-020-2876-6 (2020). source

      Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured
    • cites [32] Feng, S. et al. Dense sampling of bird diversity increases power of comparative genomics. Nature https://doi.org/10.1038/s41586-020-2873-9 (2020). source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The version of Cactus available in 2012 performed very well in the Alignathon.

    “The version of Cactus available in 2012 performed very well in the Alignathon14, an evaluation of genome aligners.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [14] Earl, D. et al. Alignathon: a competitive assessment of whole-genome alignment methods. Genome Res. 24, 2077–2089 (2014). source

  • May combine two claims.

    Premisecitation

    Cactus has neither of these restrictions; it can generate a reference-free multiple alignment that allows detection of multiple-orthology relationships.

    “Cactus6 is a genome alignment program that has neither of these restrictions; it can generate a reference-free multiple alignment that allows the detection of multiple-orthology relationships.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [6] Paten, B. et al. Cactus: algorithms for genome multiple sequence alignment. Genome Res. 21, 1512–1528 (2011). source

  • Classified as probably not a substantial claim.

    Premisecitation

    New genome assemblies have been arriving at a rapidly increasing pace, due to decreases in sequencing costs and improvements in third-generation sequencing technologies.

    “New genome assemblies have been arriving at a rapidly increasing pace, thanks to decreases in sequencing costs and improvements in third-generation sequencing technologies1–3.”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites [1] Eid, J. et al. Real-time DNA sequencing from single polymerase molecules. Science 323, 133–138 (2009). source
    • cites [2] Weisenfeld, N. I., Kumar, V., Shah, P., Church, D. M. & Jaffe, D. B. Direct determination of diploid genome sequences. Genome Res. 27, 757–767 (2017). source

      The Discussion (page unavailable) says the low cost of the authors’ assembly method makes it applicable to large-scale projects. It does not establish that new assemblies were arriving at a rapidly increasing pace, or attribute such a trend to falling sequencing costs and improvements in third-generation sequencing technologies. (LLM, conf=0.78)

      Experimental — accuracy not yet measured
    • cites [3] Jain, M., Olsen, H. E., Paten, B. & Akeson, M. The Oxford Nanopore MinION: delivery of nanopore sequencing to the genomics community. Genome Biol. 17, 239 (2016). source

      The De novo assembly section (page unavailable) describes how nanopore sequencing has enabled new assembly methods and reports a genome assembled using only MinION data. The Conclusions (page unavailable) say MinION performance improved rapidly. Neither passage establishes that new genome assemblies are arriving at a rapidly increasing pace or attributes that pace to falling sequencing costs. (LLM, conf=0.82)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Progressive alignment has been successfully applied to whole-genome alignment before, e.g., by progressiveMauve and TBA/MULTIZ.

    “Progressive alignment has been successfully applied to whole-genome alignment before—for example, by progressiveMauve21 and TBA/MULTIZ22.”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [21] Darling, A. E., Mau, B. & Perna, N. T. progressiveMauve: multiple genome alignment with gene gain, loss and rearrangement. PLoS One 5, e11147 (2010). source
    • cites [22] Blanchette, M. et al. Aligning multiple genomic sequences with the threaded blockset aligner. Genome Res. 14, 708–715 (2004). source

  • Classified as probably not a substantial claim.

    Premisecitation

    The Vertebrate Genomes Project, Genome 10K, and Earth BioGenome Project aim to release thousands of new, high-quality genome assemblies over the next decade.

    “The Vertebrate Genomes Project38 led by the Genome 10K39 and the Earth BioGenome Project40, among others, aim to release thousands of new, high-quality genome assemblies over the next decade.”
    Quote in the paperSubstantial claim3 of 3 sources checked
    • cites [38] Rhie, A. et al. Towards complete and error-free genome assemblies of all vertebrate species. Preprint at https://doi.org/10.1101/2020.05.22.110833 (2020). source
    • cites [39] Koepfli, K.-P., Paten, B., the Genome 10K Community of Scientists & O’Brien, S. J. The Genome 10K Project: a way forward. Ann. Rev. Animal Biosci. 3, 57–111 (2015). source

      The Introduction identifies Genome 10K’s goal of sequencing 10,000 vertebrate genomes and says the project facilitates release of genome data and develops assembly standards. But The Genomic Road Ahead says it is difficult to estimate how genome science will change in the next decade; it does not commit to releasing thousands of high-quality assemblies within that period. This verdict concerns the Genome 10K citation, not the separately cited projects. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [40] Lewin, H. A. et al. Earth BioGenome Project: Sequencing life for the future of life. Proc. Natl Acad. Sci. USA 115, 4325–4333 (2018) source

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

    Interpretationcitation

    As the average assembly becomes ever more complete and accurate, the value of such a reference-free approach grows.

    “As the average assembly becomes ever more complete and accurate38, the value of such a reference-free approach grows.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [38] Rhie, A. et al. Towards complete and error-free genome assemblies of all vertebrate species. Preprint at https://doi.org/10.1101/2020.05.22.110833 (2020). source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Sequencing efforts will increasingly produce multiple, phased de novo assemblies from different individuals in a population.

    “Similarly driven by technology improvements, sequencing efforts will increasingly produce multiple, phased de novo assemblies from different individuals in a population41.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [41] Shafin, K. et al. Nanopore sequencing and the Shasta toolkit enable efficient de novo assembly of eleven human genomes. Nat. Biotechnol. 38, 1044–1053 (2020). source

      The Discussion (page unavailable) reports efficient de novo assembly of 11 human genomes and anticipates that the toolkit could help produce phased assemblies. The Methods’ Sample selection section (page unavailable) describes selecting individuals to capture allelic diversity. The paper does not explicitly predict that sequencing efforts will increasingly produce multiple phased assemblies across a population; phasing is presented as a promising next step. (LLM, conf=0.82)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Alignment projection-mapping methods were previously shown to align more UTR bases than translated methods.

    “Alignment projection-mapping methods were previously shown53 to align more UTR bases than translated methods.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [53] Ondov, B. D. et al. Mash: fast genome and metagenome distance estimation using MinHash. Genome Biol. 17, 132 (2016). source

      The Background section describes Mash’s alignment-free distance estimates and compares them with alignment-based measures, but does not compare projection-mapping with translated methods. Searches for UTR bases, projection mapping, and untranslated regions found no passage addressing which method aligns more UTR bases. (LLM, conf=0.77)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The B10K and Zoonomia consortia are using this alignment for comparative analysis.

    “The B10K32 and Zoonomia31 consortia are using this alignment for comparative analysis, for example, analysing patterns of selection in unprecedented detail.”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [32] Feng, S. et al. Dense sampling of bird diversity increases power of comparative genomics. Nature https://doi.org/10.1038/s41586-020-2873-9 (2020). source
    • cites [31] Zoonomia Consortium. A comparative genomics multitool for scientific discovery and conservation. Nature https://doi.org/10.1038/s41586-020-2876-6 (2020). source

  • May combine two claims.

    Findingown data

    The alignments using the progressive strategy finished more quickly than the star strategy, with the speed improvement growing larger with increasing number of species (15% reduction in runtime for 10 species and 48% for 20 species).

    “The alignments using the progressive strategy finished more quickly, with the speed improvement growing larger with the increasing number of species (for example, a 15% reduction in runtime for 10 species and 48% for 20 species)”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The progressive strategy has linear runtime scaling, whereas the star-tree strategy has quadratic scaling.

    “owing to its linear runtime scaling, as opposed to the quadratic scaling of the star-tree”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    Progressive Cactus incorporates a progressive alignment strategy that changes the runtime to scale linearly with the number of genomes.

    “we present fundamental changes to the Cactus process that incorporate a progressive alignment strategy15, which changes the runtime of the alignment to scale linearly with the number of genomes.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [15] Feng, D. F. & Doolittle, R. F. Progressive sequence alignment as a prerequisite to correct phylogenetic trees. J. Mol. Evol. 25, 351–360 (1987). source

  • May combine two claims.

    Findingown data

    Progressive Cactus produces alignments with higher accuracy for both simulated primate (F1 score of 0.989) and mammal (F1 score of 0.795) clades than any aligner that participated in the Alignathon, including the original version of Cactus.

    “Progressive Cactus produces alignments with higher accuracy for both simulated primate (F1 score of 0.989) and mammal (F1 score of 0.795) clades than any aligner that participated in the Alignathon (Supplementary Tables 1, 2), including the original version of Cactus.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingreasoning

    Using Toil, the problem can be broken into small pieces that work in heterogeneous compute environments.

    “using Toil, we can break up the problem into small pieces that can work in heterogeneous compute environments”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Genome alignment is a computationally intensive task.

  • May combine two claims.

    Findingreasoning

    Progressive Cactus enables reference-free alignment of tens to thousands of large vertebrate genomes while maintaining high alignment quality.

    “Progressive Cactus, which enables the reference-free alignment of tens to thousands of large vertebrate genomes while maintaining high alignment quality.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Findingreasoning

    The outgroup genomes serve to answer what sequence from ingroups is present in the ancestor and in how many copies.

    “The outgroup genomes serve to answer the question of what sequence from the ingroups is also present in the ancestor (whether an indel among the ingroups is likely to be a deletion rather than an insertion), and in how many copies (whether a duplication predates or postdates the speciation event the node represents).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The F1 score for aligned pairs within the clade of Cuculus canorus, Chlamydotis macqueenii and Tauraco erythrolophus between the two alignments was 0.972, lower but comparable to the score for a similar clade with identical phylogenetic relationship in both trees, 0.982.

    “The F1 score for aligned pairs within this clade between the two alignments was 0.972, lower but comparable to the score for a similar clade that had an identical phylogenetic relationship in both trees, 0.982 (for Merops nubicus, Picoides pubescens and Buceros rhinoceros).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Progressive Cactus was used to align 605 amniote genomes, comprising more than 1 trillion bases of DNA and an estimated 35.4 neutral substitutions per site.

    “To demonstrate Progressive Cactus, we present results from an alignment of 605 amniote genomes, relating in a reference-free manner to more than 1 trillion bases of DNA across hundreds of millions of years of genome evolution (an estimated 35.4 neutral substitutions per site).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Of the aligned pairs in the induced pairwise Progressive Cactus alignments, 82% were found in the chains and nets alignment, and 78% of pairs in the chains and nets alignment were found in each Progressive Cactus alignment.

    “Of the aligned pairs in the induced pairwise Progressive Cactus alignments, 82% were found in the chains and nets alignment, and, vice versa, 78% of pairs in the chains and nets alignment were found in each Progressive Cactus alignment.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The progressive strategy is more accurate than the star strategy and maintains accuracy as the number of species increases.

    “The progressive strategy is also more accurate than the star strategy (Fig. 2b) and maintains accuracy as the number of species (and therefore nodes in the tree) increases.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingreasoning

    Progressive Cactus can be run on many different environments: single machines, conventional clusters, and commercial clouds.

    “Progressive Cactus can be run on many different environments: single machines (for small alignments), conventional clusters, and commercial clouds.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Progressive Cactus aligned more total bases to chicken (average 69.4% of the chicken genome) than MULTIZ (64.9%), for an average increase of 47 Mb.

    “Progressive Cactus aligned more total bases to chicken (covering an average of 69.4% of the chicken genome from the other species) than MULTIZ (64.9%), for an average increase of 47 Mb.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Of 84,001 transcripts, BLAT mapped 70%, BLAST mapped 80%, LASTZ mapped 67%, and Progressive Cactus mapped 74% to the chicken genome.

    “Of 84,001 transcripts, BLAT mapped 70%, BLAST mapped 80%, LASTZ mapped 67%, and Progressive Cactus mapped 74%.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingreasoning

    The amniote (human-chicken) ancestral assembly retains 16.3% of chicken intron bases versus 84.4% in the avian ancestor, and 7.2% of human intron bases versus 56.5% in the eutherian ancestor.

    “the amniote (human–chicken) ancestral assembly has a much lower proportion of reconstructed sequence than its immediate children, the avian and eutherian mammal ancestors, for example, retaining 16.3% of chicken intron bases versus 84.4% in the avian ancestor, and 7.2% of human intron bases versus 56.5% in the eutherian ancestor.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Coverage within the 600-way alignment closely tracks phylogenetic distance and genome size; median coverage on human is 2.3 Gb from Euarchonta, 1.2 Gb from Laurasiatheria, and 1.0 Gb from Glires.

    “Coverage within the 600-way alignment closely tracks phylogenetic distance and genome size; for example, a median coverage on human of 2.3 gigabases (Gb) from Euarchonta mammalian species, versus 1.2 Gb and 1.0 Gb from more distant Laurasiatheria and Glires mammalian species, respectively (Fig. 3b, c).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingreasoning

    Progressive Cactus's representation of duplication events forbids the representation of gene-tree-species-tree discordance (as in incomplete lineage-sorting or horizontal transfer) and the exact ordering of multiple duplication events along a single branch.

    “This forbids the representation of gene-tree-species-tree discordance as would occur in incomplete lineage-sorting or horizontal transfer, as well as the exact ordering of multiple duplication events along a single branch.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The relative rates of small indels to nucleotide substitutions are lower for insertions (1.2% of the substitution rate for both clades) and for deletions (2.4% for avians and 1.2% for eutherians).

    “although the relative rates remained lower for insertions (1.2% of the substitution rate for both clades) and for deletions (2.4% and 1.2% of the substitution rate for avians and eutherians, respectively)”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Best-hit filtering removes many more probably paralogous alignments than single-copy outgroup filtering, especially to closely related genomes, while leaving approximately the same amount of sequence covered by at least one alignment.

    “Of the two methods, the newer best-hit filtering removes many more probably paralogous alignments, especially to closely related genomes, while leaving approximately the same amount of sequence covered by at least one alignment.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    There is evidence of a slightly increased rate of insertions in avians.

    “but evidence of a slightly increased rate of insertions in avians (Extended Data Fig. 3a)”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Both genome-addition methods, as well as the full alignment, achieved an F1 score of 0.926, with accuracy deviating less than 0.1% from the full alignment that included the macaque from the start.

    “Both methods resulted in alignments that had accuracy deviating less than 0.1% from the full alignment that included the macaque from the start: both addition methods, as well as the full alignment, achieved an F1 score of 0.926 (Extended Data Table 1).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Findingreasoning

    The biology of overlapping gene structures and the ambiguities in defining genes cause around 4% of genomic bases to appear in more than one gene in the RNA, and 3% in the CDS gene sets owing to overlap.

    “The biology of overlapping gene structures and the ambiguities in defining genes cause around 4% of genomic bases to appear in more than one gene in the RNA, and 3% in the CDS gene sets owing to overlap.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    All ancestors up to human-rhesus had over 78% of the human complement of L1PA6 elements.

    “All ancestors up to human-rhesus had over 78% of the human complement of L1PA6 elements (Supplementary Fig. 10).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingreasoning

    Progressive Cactus alignments are capable of representing complex orthology/paralogy relationships, with an ability to display alignments labelled as orthologous and an option to request alignments to paralogues at a customizable divergence-time threshold.

    “For this reason, Progressive Cactus alignments are capable of representing complex orthology/paralogy relationships, with an ability to display the alignment(s) labelled as orthologous, but also the option for a user to request alignments to paralogues at a customizable divergence-time threshold.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In a comparison of best-hit filtering and single-copy outgroup filtering, the amount of human sequence mapping to two or more places in the chimpanzee genome was reduced from 6.1% to 2.6%, while the total amount of human covered by chimpanzee increased.

    “Comparing the best-hit filtering alignment and the one using the single copy outgroup filtering, the amount of human sequence mapping to two or more places in the chimpanzee genome was reduced from 6.1% to 2.6%, while the total amount of human covered by chimpanzee actually increased owing to the removal of ancient homologues, simplifying the initial alignment relationships (see Extended Data Fig.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The ancestral reconstructions within the 600-way alignment are highly complete, especially for functional sequence: 86% of human coding bases are represented in the reconstruction of the ancestor of all placental mammals, and 95% of chicken coding bases are represented in the reconstruction of the common ancestor of avians.

    “The ancestral reconstructions within the 600-way alignment are highly complete, especially for functional sequence: 86% of human coding bases are represented in our reconstruction of the ancestor of all placental mammals, whereas 95% of chicken coding bases are represented in our reconstruction of the common ancestor of avians (Fig. 3d, e).”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisenone given

    Progressive aligners use a guide tree to recursively break a multiple alignment problem into smaller sub-alignments, each solved independently, and then aligned together according to the tree structure.

    “Progressive aligners use a ‘guide tree’ to recursively break a multiple alignment problem into many smaller sub-alignments, each of which is solved independently; the resulting sub-alignments are themselves aligned together according to the tree structure to create the final alignment.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisenone given

    Two common limitations of aligners are reference bias and single-copy restriction.

    “Two of the most common limitations are ‘reference bias’, the result of constraining a multiple alignment to only regions present in a single reference genome, and restricting the alignment to be ‘single-copy’, which allows only a single alignment in any column in any given genome, causing the alignment to miss multiple-orthology relationships created by lineage-specific duplications.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Premisenone given

    The progressive approach means that the alignment between two genomes distant in the guide tree is informed by the reconstructions of the ancestral genomes along the path, which is in turn formed using data from other genomes in the tree.

    “Our progressive approach means that the alignment between two genomes distant in the guide tree is informed by the reconstructions of the ancestral genomes along the path, which is in turn formed using data from other genomes in the tree.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    The avian species tree is still being actively debated and there are different plausible hypotheses, making birds an excellent test case with no single clearly correct guide tree.

    “The avian species tree is still being actively debated28,29 and there are different plausible hypotheses, making birds an excellent test case with no single clearly correct guide tree.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [28] Prum, R. O. et al. A comprehensive phylogeny of birds (Aves) using targeted next-generation DNA sequencing. Nature 526, 569–573 (2015). source
    • cites [29] Jarvis, E. D. et al. Whole-genome analyses resolve early branches in the tree of life of modern birds. Science 346, 1320–1331 (2014). source

  • Classified as probably not a substantial claim.

    Premisenone given

    Many genome aligners intentionally limit the alignments they produce to simplify the problem.

    “many intentionally limit the alignments they produce to simplify the problem.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisenone given

    HAL does not produce a fully binarized history of duplication events.

    “Because HAL does not produce a fully binarized history of duplication events, we compared the MRCA of randomly selected pairs of sites from genomes containing a duplication within the column.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    The computational cost of iteratively aligning each ingroup against one outgroup at a time is far less than naively aligning against the entire outgroup set, while still retaining nearly all of the benefit.

    “In this way, the computational cost is reduced to be far less than naively aligning against the entire outgroup set, while still retaining nearly all of the benefit.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Any region already containing an outgroup alignment benefits very little from aligning an additional outgroup.

  • May combine two claims.

    Interpretationreasoning

    The coverage increase probably reflects that losses caused by not removing recoverable chains in any single subproblem are relatively small but can compound to be considerable in large alignments, since many subproblems are involved in creating the alignment between distant species.

    “This probably reflects the fact that though the losses caused by not removing recoverable chains in any single subproblem are relatively small, they can compound to be quite considerable in large alignments since many subproblems are involved in creating the alignment between distant species (such as human and mouse, which are separated by seven internal nodes in this tree).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Interpretationnone given

    Primary alignments represent the most likely orthologue relationship (or in the case of multiple orthology, probably a random orthologue).

    “All primary alignments are added to the initial graph unconditionally because they represent the most likely orthologue relationship (or in the case of multiple orthology, probably a random orthologue) (Supplementary Fig. 15).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Incomplete blocks become more prevalent at longer evolutionary distances, because the local aligner misses more true homologies at increasing distances, causing more incomplete blocks and in turn a far worse alignment.

    “These problematic incomplete blocks become more prevalent at longer evolutionary distances: the local aligner will miss more true homologies at increasing distances, causing more incomplete blocks and in turn a far worse alignment.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    Unrecoverable blocks represent a minimal set of anchors that can be extended from to recover the alignment relationships from the original sequence graph as well as potential additional alignment relationships.

    “these unrecoverable blocks represent a minimal set of anchors that can be extended from to recover the alignment relationships from the original sequence graph as well as potential additional alignment relationships.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductreasoning

    The ancestral base-calls are generated as the alignment is being made, so they necessarily take only part of the alignment information into account and may differ from the ideal base-calls that would use information across the entire alignment.

    “These base-calls are generated as the alignment is being made, so they necessarily take only a part of the alignment information into account and may be different than the ideal base-calls would be if taking into account information across the entire alignment.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisenone given

    The original CAF algorithm was focused on removing small rearrangements while retaining as much of the original alignment relationships as possible in the filtered cactus graph.

    “The original CAF algorithm was focused on removing small rearrangements while retaining as much of the original alignment relationships as possible in the filtered cactus graph.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S2 (checkable).

    Premisereasoning

    These projects will need massive genome alignments.

    “These projects will give us incredible insight into natural history, but will need massive genome alignments.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Best-hit filtering allows lineage-specific duplications of ingroup genomes to correctly land in the same block, while avoiding merging blocks from likely-paralogous alignments.

    “this allows lineage-specific duplications of ingroup genomes to correctly land in the same block, while avoiding merging blocks from likely-paralogous alignments.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    The experiments were not randomized, and there was no blinding.

    “The experiments were not randomized, and there was no blinding.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Incomplete blocks remain incomplete because once a block becomes an anchor it can never be modified, so they prevent the true alignment relationship from being found even if an adjacent syntenic anchor block is complete.

    “As a result, these incomplete blocks will remain incomplete: they prevent the true alignment relationship from being found, even if an adjacent syntenic anchor block is complete and contains all desired alignment relationships.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Sample selection was made according to the needs of the Zoonomia and B10K projects.

    “Sample selection was made according to the needs of the Zoonomia and B10K projects.”
    Quote in the paperNot a substantial claim
58 of 58

  • The paper relies on this without support.

    The existing implementation of Cactus struggles in regions of highly duplicated sequences.

    “and struggles in regions of highly duplicated sequences.”

  • The paper relies on this without support.

    Genome alignment is a computationally intensive task.

    “Although genome alignment is a computationally intensive task”

  • The paper relies on this without support.

    Any region already containing an outgroup alignment benefits very little from aligning an additional outgroup.

    “we note that in general any region already containing an outgroup alignment benefits very little from aligning an additional outgroup.”

  • The paper relies on this without support.

    Unmasked repetitive sequence can negatively affect alignment runtimes and quality.

    “often repetitive sequence goes unmasked due to poor masking or incomplete repeat libraries for newly-sequenced species. This can negatively affect alignment runtimes (as alignments need to be enumerated to and from all copies of a repetitive sequence) and impact quality.”

  • The paper relies on this without support.

    The approximately maximum-likelihood trees independently re-estimated by FastTree from the same regions are accurate enough to serve as a reference against which errors in the HAL trees can be detected.

    “we compared phylogenetic trees implicit in the columns of HAL alignments to independently re-estimated approximately maximum likelihood (ML) trees produced by FastTree (http://www.microbesonline.org/fasttree/, version 2.1.11)57 for the same regions.”
5 of 5

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?

  • Progressive Cactus generally has a time complexity of O(n^2 lg n) for aligning n genomes.

    “It generally has a time complexity of O ( n 2 lg n ) for aligning n genomes.”

    From Whole-Genome Alignment: Methods, Challenges, and Future Directions (2024) · cites this paper as [49]

    The Main section says Progressive Cactus changes alignment runtime to scale linearly with the number of genomes, contrary to the claimed O(n² lg n) scaling. The Evaluation on simulated data section assigns quadratic scaling to the non-progressive strategy instead. No page numbers are provided in our copy. (LLM, conf=0.92)

    Checked by a reasoning model — may be wrong.

    Experimental — accuracy not yet measured

  • The use of a graph-based method allows Progressive Cactus to efficiently manage and process complex genomic alignments through representing sequences and their relationships in a dynamic, scalable structure.

    “The use of a graph-based method allows Progressive Cactus to efficiently manage and process complex genomic alignments through representing sequences and their relationships in a dynamic, scalable structure.”

    From Whole-Genome Alignment: Methods, Challenges, and Future Directions (2024) · cites this paper as [49]

    The Methods sections on Progressive Cactus and paralogy resolution describe a sequence graph that represents alignments and is updated as alignment blocks are added. But the Main section and Evaluation on simulated data attribute efficient scaling with the number of genomes to the progressive alignment strategy, not to the graph structure; the claimed causal link is unsupported. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Progressive Cactus undergoes iterative refinement as new genomes are added, optimizing the graph structure based on sequence homologies and structural constraints.

    “The existing graph undergoes iterative refinement as new genomes are added, optimizing the graph structure based on sequence homologies and structural constraints;”

    From Whole-Genome Alignment: Methods, Challenges, and Future Directions (2024) · cites this paper as [49]

    The Methods section, “Adding a new genome to an existing alignment” (page not provided), says genomes can be added to an existing alignment, including iteratively. The Progressive Cactus and Paralogy resolution passages describe refining alignments and accepting or rejecting sequence-homology links when constructing a graph. They do not describe repeatedly optimizing the existing graph as each genome is added; instead, adding a genome generally involves localized alignments, with at most one ancestral sequence re-inferred. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Progressive Cactus iterates through the alignment process multiple times, refining the alignment graph at each step.

    “Progressive Cactus iterates through the alignment process multiple times, refining the alignment graph at each step;”

    From Whole-Genome Alignment: Methods, Challenges, and Future Directions (2024) · cites this paper as [49]

    The Methods sections describe iterative changes to the sequence graph: CAF filters local alignments, and paralogy resolution adds alignments one at a time. The Progressive Cactus section also says BAR refines an initial alignment. These passages do not describe repeatedly running the entire alignment process or refining the alignment graph at every step. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Cactus uses a graph-based approach to combine sets of pairwise alignments obtained from lastz into a multiple genome alignment.

    “Cactus is a tool that uses a graph-based approach to combine sets of pairwise alignments obtained from lastz into a multiple genome alignment37.”

    From A draft human pangenome reference. (2023) · cites this paper as [37]

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.

  • Micro-indel cutoff differs between Results and Methods

    Minor

    The Results include insertion and deletion events of 20 bp, while the Methods say only events shorter than 20 bp were counted.

1 of 1

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Authors
Armstrong, J., Hickey, G., Diekhans, M., Fiddes, I. T., Novak, A. M., Deran, A., Fang, Q., Xie, D., Feng, S., Stiller, J., Genereux, D., Johnson, J., Marinescu, V. D., Alföldi, J., Harris, R. S., Lindblad-Toh, K., Haussler, D., Karlsson, E., Jarvis, E. D., Zhang, G., & Paten, B.
Affiliations
  • University of California, Santa Cruz (US)
  • University of Copenhagen (DK)
  • University of Chinese Academy of Sciences (CN)
  • Kunming Institute of Zoology (CN)
  • Broad Institute (US)
  • Uppsala University (SE)
  • Pennsylvania State University (US)
  • Howard Hughes Medical Institute (US)
Corresponding author
  • Zhang, Guojie
  • Paten, Benedict
ORCID
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2020-11-11
Volume
587
Issue
7833
Pages
246-251
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/s41586-020-2871-y
PMC
PMC7673649
OpenAlex
W3100651612
Cited by
586
References
66
Citations by year
2026: 96 · 2025: 132 · 2024: 128 · 2023: 100 · 2022: 85 · 2021: 27 · 2020: 17 · 2019: 1
FWCI
19.29
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by)
  • eScholarship@UMassChan (submittedVersion, cc-by)
  • KTH Publication Database DiVA (KTH Royal Institute of Technology) (submittedVersion, other-oa)
  • RePEc: Research Papers in Economics (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
Funders
  • Villum Fonden (00025900)
  • National Institutes of Health
  • National Heart, Lung, and Blood Institute (U01HL137183)
  • National Human Genome Research Institute (R01HG009737, R01HG010485, R01HG008742, U01HG010971, T32HG008345, U41HG007234, U54HG007990, U01HG010961, U24HG007234, U41HG010972)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genome Rearrangement Algorithms
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
Keywords
multiple genome alignment, structural variants, genome evolution
MeSH terms
Amnion, Animals, Computer Simulation, Haplotypes, Humans, Quality Control, Software, Vertebrates, Sequence Alignment, Genome, Genomics

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.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-11-02.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-11-02.

Cited sources are checked by 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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