A computational framework to assess genome-wide distribution of polymorphic human endogenous retrovirus-K In human populations
Identifieur interne : 000731 ( Main/Exploration ); précédent : 000730; suivant : 000732A computational framework to assess genome-wide distribution of polymorphic human endogenous retrovirus-K In human populations
Auteurs : Weiling Li [États-Unis] ; Lin Lin [États-Unis] ; Raunaq Malhotra [États-Unis] ; Lei Yang [États-Unis] ; Raj Acharya [États-Unis] ; Mary Poss [États-Unis]Source :
- PLoS Computational Biology [ 1553-734X ] ; 2019.
Descripteurs français
- KwdFr :
- MESH :
English descriptors
- KwdEn :
- MESH :
- genetics : Continental Population Groups, Endogenous Retroviruses, Genome, Human, Genome, Viral, Proviruses.
- methods : Genetics, Population, Genomics.
- Algorithms, Humans, Molecular Epidemiology, Software.
Abstract
Human Endogenous Retrovirus type K (HERV-K) is the only HERV known to be insertionally polymorphic; not all individuals have a retrovirus at a specific genomic location. It is possible that HERV-Ks contribute to human disease because people differ in both number and genomic location of these retroviruses. Indeed viral transcripts, proteins, and antibody against HERV-K are detected in cancers, auto-immune, and neurodegenerative diseases. However, attempts to link a polymorphic HERV-K with any disease have been frustrated in part because population prevalence of HERV-K provirus at each polymorphic site is lacking and it is challenging to identify closely related elements such as HERV-K from short read sequence data. We present an integrated and computationally robust approach that uses whole genome short read data to determine the occupation status at all sites reported to contain a HERV-K provirus. Our method estimates the proportion of fixed length genomic sequence (
Url:
DOI: 10.1371/journal.pcbi.1006564
PubMed: 30921327
PubMed Central: 6456218
Affiliations:
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Le document en format XML
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<front><div type="abstract" xml:lang="en"><p>Human Endogenous Retrovirus type K (HERV-K) is the only HERV known to be insertionally polymorphic; not all individuals have a retrovirus at a specific genomic location. It is possible that HERV-Ks contribute to human disease because people differ in both number and genomic location of these retroviruses. Indeed viral transcripts, proteins, and antibody against HERV-K are detected in cancers, auto-immune, and neurodegenerative diseases. However, attempts to link a polymorphic HERV-K with any disease have been frustrated in part because population prevalence of HERV-K provirus at each polymorphic site is lacking and it is challenging to identify closely related elements such as HERV-K from short read sequence data. We present an integrated and computationally robust approach that uses whole genome short read data to determine the occupation status at all sites reported to contain a HERV-K provirus. Our method estimates the proportion of fixed length genomic sequence (<italic>k-mers</italic>
) from whole genome sequence data matching a reference set of <italic>k-mers</italic>
unique to each HERV-K locus and applies mixture model-based clustering of these values to account for low depth sequence data. Our analysis of 1000 Genomes Project Data (KGP) reveals numerous differences among the five KGP super-populations in the prevalence of individual and co-occurring HERV-K proviruses; we provide a visualization tool to easily depict the proportion of the KGP populations with any combination of polymorphic HERV-K provirus. Further, because HERV-K is insertionally polymorphic, the genome burden of known polymorphic HERV-K is variable in humans; this burden is lowest in East Asian (EAS) individuals. Our study identifies population-specific sequence variation for HERV-K proviruses at several loci. We expect these resources will advance research on HERV-K contributions to human diseases.</p>
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<affiliations><list><country><li>États-Unis</li>
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<region><li>Indiana</li>
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