The DOI matches its Crossref record; 40 of the 40 references it cites were found in a registry or an index; none of the 28 sources its claims cite is checked for support yet.
The case for not masking away repetitive DNA
Open accessAbstract
In the course of analyzing whole-genome data, it is common practice to mask or filter out repetitive regions of a genome, such as transposable elements and endogenous retroviruses, in order to focus only on genes and thus simplify the results. This Commentary is a plea from one member of the Mobile DNA community to all gene-centric researchers: please do not ignore the repetitive fraction of the genome . Please stop narrowing your findings by only analyzing a minority of the genome, and instead broaden your analyses to include the rich biology of repetitive and mobile DNA. In this article, I present four arguments supporting a case for retaining repetitive DNA in your genome-wide analysis.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
This Commentary argues that gene-centric researchers should stop masking or filtering repetitive DNA from genome-wide analyses, because transposable elements and endogenous retroviruses contribute to gene regulation, evolution, disease, and technology development. It presents four arguments for retaining repetitive DNA and notes that improved sequencing and mapping tools now make such analyses feasible.
Key findings
- “Whole-genome” datasets are routinely restricted to the non-repetitive portion of the human genome, reported as 22–51% by RepeatMasker, leaving 78–49% of the genome unanalyzed in favor of simplified gene expression evaluation.
- Repetitive and mobile DNA can regulate single genes and entire gene regulatory networks, act as developmental/tissue-stage-specific markers, produce long non-coding RNAs, sense cellular stress, contribute to centromere function, substitute as telomeres, and associate with several diseases.
- The paper argues technology has advanced: Illumina SBS read lengths transitioned from 50 to 150 nucleotides, and PacBio/Nanopore long reads remove much mapping ambiguity; tools such as MELT, RetroSeq, EpiTEome, McClintock, T-lex, Clari-TE, and TEtoolkit/TEtranscripts can assay repetitive DNA.
- Mobile DNA research has produced or inspired research tools including mutagenesis/gene tagging, transgenesis, gene trapping, ATAC-seq, tagmentation, and CRISPR-Cas genome editing.
Methods
- This is a Commentary, not primary research; no experimental design, sample, dataset, or statistical analysis is reported.
- The author presents four arguments supporting retention of repetitive DNA in genome-wide analyses and cites prior literature, tools, and examples rather than generating new data.
Limitations
- The paper states it is a short Commentary and that “too many examples exist to fit into this short Commentary article.”
- Evident from the text: it is a persuasive perspective from a Mobile DNA researcher, with no systematic literature review, no new empirical data, and no quantitative evaluation of masking practices.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
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Verification
Claims the paper makes
16 No basis given · 14 Check pending · 7 Own interpretation · 3 Not checked yet · 2 No full text of the sources
In the paper
“Even the key enabling technology of this decade, CRISPR-Cas genome editing, is now understood to be based upon mobile DNA [38].”
What the sources say
- Check pendingcites [38] Koonin EV, Makarova KS. Mobile Genetic Elements and Evolution of CRISPR-Cas Systems: All the Way There and Back. Genome Biol Evol. 2017;9:2812–25. source
plaindirect- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The significantly longer reads of PacBio and Nanopore sequencing approaches altogether remove the mapping ambiguity that has previously limited the genome-wide analysis of repetitive DNA.”
boosteddirect- Asserted: passes — The authors put it forward as true.
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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
“Therefore, if a researcher were performing a ChIPseq experiment to identify where a transcription factor binds (for example), or a chromosome confirmation capture (4C/HiC) experiment to identify enhancer-promoter interactions, they would potentially miss important enhancers if repetitive DNA was filtered from their analysis.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Mobile DNA biology has enabled improved mutagenesis and gene tagging, transgenesis, and analysis of gene function by gene trapping, just to name a few [35].”
What the sources say
- Check pendingcites [35] Ivics Z, Li MA, Mátés L, Boeke JD, Nagy A, Bradley A, et al. Transposon-mediated genome manipulation in vertebrates. Nat Methods. 2009;6:415–22. source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“TEs and ERVs can act as developmental and tissue stagespecific markers (such as in early mammalian development [8, 9])”
What the sources say
- Check pendingcites [8] Macfarlan TS, Gifford WD, Driscoll S, Lettieri K, Rowe HM, Bonanomi D, et al. Embryonic stem cell potency fluctuates with endogenous retrovirus activity. Nature. 2012;487:57–63. source
- Check pendingcites [9] Gerdes P, Richardson SR, Mager DL, Faulkner GJ. Transposable elements in the mammalian embryo: pioneers surviving through stealth and service. Genome Biol. 2016;17:1286. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Repetitive and mobile DNA provide a rich source of gene regulation, evolutionary flexibility and epigenetic catalysts.”
What the sources say
- Check pendingcites [4] Chuong EB, Elde NC, Feschotte C. Regulatory activities of transposable elements: from conflicts to benefits. Nat Rev Genet. 2017;18:71–86. source
- Not checked — no full text of the sourcecites [5] McCue AD, Slotkin RK. Transposable element small RNAs as regulators of gene expression. Trends Genet. 2012;28:616–23. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“and as sensors of cellular stress [11]”
What the sources say
- Not checked — no full text of the sourcecites [11] Horváth V, Merenciano M, Gonzalez J. Revisiting the Relationship between Transposable Elements and the Eukaryotic Stress Response. Trends Genet. 2017;33:832–41. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“as sources of long non-coding RNAs [10]”
What the sources say
- Not checked yetcites [10] Kapusta A, Kronenberg Z, Lynch VJ, Zhuo X, Ramsay L, Bourque G, et al. Transposable Elements Are Major Contributors to the Origin, Diversification, and Regulation of Vertebrate Long Noncoding RNAs. PLoS Genet. 2013;9:e1003470. source
plaindirect- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“In contrast to software advances, the key enabling technology that has enhanced the read mappability (and therefore coverage) of the repetitive fraction of the genome is improved read length.”
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The structural variation map of 2504 genomes that specifically identified Alu , L1 and SVA mobile element insertions across human populations [39]”
What the sources say
- Not checked yetcites [39] Sudmant PH, Rausch T, Gardner EJ, Handsaker RE, Abyzov A, Huddleston J, et al. An integrated map of structural variation in 2,504 human genomes. Nature. 2015;526:75–81. source
plain- Asserted: passes — The authors put it forward as true.
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- Probably not a substantial claim. 10
- It may state two separate claims as one. 9
In the paper
“For example, one of the most important discoveries from my own career came from reanalyzing available microarray data for TE expression [3].”
What the sources say
- Check pendingcites [3] Slotkin RK, Vaughn M, Borges F, Tanurdzic M, Becker JD, Feijó JA, et al. Epigenetic reprogramming and small RNA silencing of transposable elements in pollen. Cell. 2009;136:461–72. source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Many researchers simply and completely filter out repetitive DNA from their analysis, even though read mapping technologies have evolved or have been specifically designed to efficiently assay repetitive DNA from whole genome data.”
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“a ChIP-seq analysis discovered that ERVs have spread interferoninducible enhancer elements and shaped the evolution of innate immunity [7].”
What the sources say
- Not checked yetcites [7] Chuong EB, Elde NC, Feschotte C. Regulatory evolution of innate immunity through co-option of endogenous retroviruses. Science. 2016;351:1083–7. source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Many published datasets exist that can be downloaded and for the first time analyzed for TE or ERV dynamics.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“This problem is most severe for small RNA biology or when only a sequence tag can be obtained, as a large fraction of the reads cannot be mapped to a unique position in the genome because only 15-30 nucleotides of sequence information is available.”
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“TEs and ERVs are now known to regulate single genes as well as entire gene regulatory networks [6, 7].”
What the sources say
- Check pendingcites [6] Sundaram V, Cheng Y, Ma Z, Li D, Xing X, Edge P, et al. Widespread contribution of transposable elements to the innovation of gene regulatory networks. Genome Res. 2014;24:1963–76. source
- Not checked yetcites [7] Chuong EB, Elde NC, Feschotte C. Regulatory evolution of innate immunity through co-option of endogenous retroviruses. Science. 2016;351:1083–7. source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“By focusing on only a fraction of the genome, only a fraction of discoveries can be made.”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
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Probably not a substantial claim. It may be too vague to check against evidence. The paper may give no reason why it holds.
In the paper
“Importantly, TEs and ERVs are both associated with (and could be the primary cause of) several diseases [15 -17].”
What the sources say
- Not checked yetcites [15] Reilly MT, Faulkner GJ, Dubnau J, Ponomarev I, Gage FH. The role of transposable elements in health and diseases of the central nervous system. J Neurosci. 2013;33:17577–86. source
- Check pendingcites [16] Wylie A, Jones AE, Abrams JM. p53 in the game of transposons. BioEssays. 2016;38:1111–6. source
- Not checked — no full text of the sourcecites [17] Burns KH. Transposable elements in cancer. Nat Rev Cancer. 2017;17:415–24. source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Because of their limited sequenced read length, deep sequencing technologies such as Illumina SBS have fundamentally superior performance for single-copy genic regions compared to repetitive DNA.”
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Confining an analysis to only part of the genome significantly restricts the likelihood and scope of the ensuing discoveries.”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“On the widely-used Illumina SBS platform, the standard read length has transitioned from 50 to 150 nucleotides, and when coupled with a paired-end sequencing and mapping approach, coverage of the non-genic portion of the genome has greatly improved.”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
It may state two separate claims as one.
In the paper
“In vitro TE systems have been leveraged to generate protocols to assay chromatin accessibility (ATAC-seq) [36] as well as efficient deep sequencing library production (tagmentation) [37].”
What the sources say
- Not checked yetcites [36] Buenrostro JD, Wu B, Chang HY, Greenleaf WJ. ATAC-seq: A Method for Assaying Chromatin Accessibility Genome-Wide. Curr Protoc Mol Biol. 2015;109:21.29.1–9. source
- Check pendingcites [37] Picelli S, Björklund AK, Reinius B, Sagasser S, Winberg G, Sandberg R. Tn5 transposase and tagmentation procedures for massively scaled sequencing projects. Genome Res. 2014;24:2033–40. source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“For example, in RNA-seq experiments researchers commonly only consider reads aligned to defined genic exons. This leaves 78-49% of the genome unanalyzed in favor of a simplified evaluation of gene expression.”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Termed ' controlling elements ' by McClintock for their roles in developmental regulation, TEs were first disregarded, then relegated as an oddity, and are now largely overlooked by most researchers.”
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“In single-locus experiments, this bias is propagated by alignment tools such as BLAST that mask low complexity and repetitive regions as a default option.”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“In fact, many of us in the Mobile DNA field have enriched our careers by making discoveries from reanalyzing publicly available data in which the original authors did not pay attention to the repetitive fraction of their data.”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
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 idea behind this approach is that we already know that some individual TE elements generate reads (by using the uniquely mapping reads), so it is most likely that these same TEs are also the producers of the multi-mapping reads.”
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Today, most biologists believe mobile DNA represents filler (or even worse: ' junk ' ) between exons or genes.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
Citations
Cites
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Repbase Update, a database of repetitive elements in eukaryotic genomes
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An integrated map of structural variation in 2,504 human genomes
Sudmant, P. H., Rausch, T., Gardner, E. J., Handsaker, R. E., Abyzov, A., Huddleston, J., Zhang, Y., Ye, K., Jun, G., Hsi-Yang Fritz, M., et al. (2015) · Nature · doi:10.1038/nature15394 · Cited by 2,354
Regulatory activities of transposable elements: from conflicts to benefits
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Repetitive Elements May Comprise Over Two-Thirds of the Human Genome
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Paired-end mappability of transposable elements in the human genome
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Extracellular vesicle-associated repetitive element DNAs as candidate osteosarcoma biomarkers
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On the Importance to Acknowledge Transposable Elements in Epigenomic Analyses
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Engines of change: Transposable element mutation rates are high and variable within Daphnia magna
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Transcriptional enhancers: from prediction to functional assessment on a genome-wide scale
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Methods and Developments in Graphical Pangenomics
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TE Density: a tool to investigate the biology of transposable elements
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Helitron and CACTA DNA transposons actively reshape the common wheat - AK58 genome
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Dynamic LTR retrotransposon transcriptome landscape in septic shock patients
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Sequence deeper without sequencing more: Bayesian resolution of ambiguously mapped reads
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Study of VIPER and TATE in kinetoplastids and the evolution of tyrosine recombinase retrotransposons
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ExplorATE: a new pipeline to explore active transposable elements from RNA-seq data
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The flax genome reveals orbitide diversity
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Comparative Evolutionary Genomics in Insects
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Impact of Acute Endurance Exercise on Alternative Splicing in Skeletal Muscle
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MGERT: a pipeline to retrieve coding sequences of mobile genetic elements from genome assemblies
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Analyzing DNA-Immunoprecipitation Sequencing Data
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Rapid evolution of a large structural polymorphism during a bacterial epidemic
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SwarmGenomics : A Unified Pipeline for Individual‐Based Whole‐Genome Analyses
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geneML: Gene annotation across diverse fungal species using deep learningPreprint
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rAAV Integration: Detection and Risk Assessment
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Additional file 3 of The flax genome reveals orbitide diversity
Song, Z., Burbridge, C., Schneider, D. J., Sharbel, T. F., & Reaney, M. J. T. (2022) · Figshare · doi:10.6084/m9.figshare.20367124
Additional file 1 of The flax genome reveals orbitide diversity
Song, Z., Burbridge, C., Schneider, D. J., Sharbel, T. F., & Reaney, M. J. T. (2022) · Figshare · doi:10.6084/m9.figshare.20367118
Additional file 1 of TE Density: a tool to investigate the biology of transposable elements
Teresi, S. J., Teresi, M. B., & Edger, P. P. (2022) · Figshare · doi:10.6084/m9.figshare.19588917
Additional file 5 of The flax genome reveals orbitide diversity
Song, Z., Burbridge, C., Schneider, D. J., Sharbel, T. F., & Reaney, M. J. T. (2022) · Figshare · doi:10.6084/m9.figshare.20367130
Additional file 2 of The flax genome reveals orbitide diversity
Song, Z., Burbridge, C., Schneider, D. J., Sharbel, T. F., & Reaney, M. J. T. (2022) · Figshare · doi:10.6084/m9.figshare.20367121
Additional file 4 of The flax genome reveals orbitide diversity
Song, Z., Burbridge, C., Schneider, D. J., Sharbel, T. F., & Reaney, M. J. T. (2022) · Figshare · doi:10.6084/m9.figshare.20367127
Additional file 6 of The flax genome reveals orbitide diversity
Song, Z., Burbridge, C., Schneider, D. J., Sharbel, T. F., & Reaney, M. J. T. (2022) · Figshare · doi:10.6084/m9.figshare.20367133
Creating and analysing an African pan-genome
Bourn, J. J. (2022) · Open University of Cape Town (University of Cape Town)
Epigenetic control of transposable elements in brain and brain disorders
Smith, C. A., & Hamilton, P. J. (2026) · Epigenetics · doi:10.1080/15592294.2026.2732514
Femenias, M. M. (2023) · Repositorio Digital de la UNC (National University of Cordoba)
Metadata
- Authors
- Slotkin, R. K.
- Affiliations
- The Ohio State University (US)
- Corresponding author
- Slotkin, R. Keith
- ORCID
- Slotkin, R. Keith
- Venue
- Mobile DNA
- Published
- 2018-05-01
- Volume
- 9
- Issue
- 1
- Pages
- 15-15
- ISSN
- 1759-8753 (ISSN-L)
- PMC
- PMC5930866
- OpenAlex
- W2805084391
- Semantic Scholar
- dc1cbd87aadf18d4e5681e7722b0f78c261307b0
- Cited by
- 61
- References
- 40
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 3 · 2023: 4 · 2022: 15 · 2021: 7 · 2020: 12 · 2019: 11 · 2018: 2
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Mobile DNA (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed (publishedVersion)
- PubMed Central (publishedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- National Science Foundation (MCB-1252370, MCB-1608392, IOS-1340050)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Chromosomal and Genetic Variations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Keywords
- repetitive DNA, transposable elements, endogenous retroviruses, genome-wide analysis, whole genome sequencing, non-coding genome
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