Diminishing return for increased Mappability with longer sequencing reads: implications of the k-mer distributions in the human genome
Identifieur interne : 001C81 ( Main/Exploration ); précédent : 001C80; suivant : 001C82Diminishing return for increased Mappability with longer sequencing reads: implications of the k-mer distributions in the human genome
Auteurs : Wentian Li [États-Unis] ; Jan Freudenberg [États-Unis] ; Pedro Miramontes [Mexique]Source :
- BMC Bioinformatics [ 1471-2105 ] ; 2014.
Descripteurs français
- KwdFr :
- MESH :
English descriptors
- KwdEn :
- MESH :
- genetics : Genome, Human.
- methods : Chromosome Mapping, Genomics, Sequence Analysis, DNA.
- Humans, Sequence Alignment.
Abstract
The amount of non-unique sequence (non-singletons) in a genome directly affects the difficulty of read alignment to a reference assembly for high throughput-sequencing data. Although a longer read is more likely to be uniquely mapped to the reference genome, a quantitative analysis of the influence of read lengths on mappability has been lacking. To address this question, we evaluate the
We observe that the proportion of non-singletons
Read mappability as measured by the proportion of singletons increases steadily up to the length scale around 200 bp. When read length increases above 200 bp, smaller gains in mappability are expected. Moreover, the proportion of non-singletons decreases with read lengths much slower than linear. Even a read length of 1000 bp would not allow the unique alignment of reads for many coding regions of human genes. A mix of techniques will be needed for efficiently producing high-quality data that cover the complete human genome.
Url:
DOI: 10.1186/1471-2105-15-2
PubMed: 24386976
PubMed Central: 3927684
Affiliations:
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Le document en format XML
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Diminishing return for increased Mappability with longer sequencing reads: implications of the <italic>k</italic>
-mer distributions in the human genome</title>
<author><name sortKey="Li, Wentian" sort="Li, Wentian" uniqKey="Li W" first="Wentian" last="Li">Wentian Li</name>
<affiliation wicri:level="1"><nlm:aff id="I1">The Robert S. Boas Center for Genomics and Human Genetic, The Feinstein Institute for Medical Research, North Shore LIJ Health System, 350 Community Drive, Manhasset, USA</nlm:aff>
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<author><name sortKey="Freudenberg, Jan" sort="Freudenberg, Jan" uniqKey="Freudenberg J" first="Jan" last="Freudenberg">Jan Freudenberg</name>
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<series><title level="j">BMC Bioinformatics</title>
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<term>Genomics (methods)</term>
<term>Humans</term>
<term>Sequence Alignment</term>
<term>Sequence Analysis, DNA (methods)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Alignement de séquences</term>
<term>Analyse de séquence d'ADN ()</term>
<term>Cartographie chromosomique ()</term>
<term>Génome humain (génétique)</term>
<term>Génomique ()</term>
<term>Humains</term>
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<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Genome, Human</term>
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<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Génome humain</term>
</keywords>
<keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Chromosome Mapping</term>
<term>Genomics</term>
<term>Sequence Analysis, DNA</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Humans</term>
<term>Sequence Alignment</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Alignement de séquences</term>
<term>Analyse de séquence d'ADN</term>
<term>Cartographie chromosomique</term>
<term>Génomique</term>
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<front><div type="abstract" xml:lang="en"><sec><title>Background</title>
<p>The amount of non-unique sequence (non-singletons) in a genome directly affects the difficulty of read alignment to a reference assembly for high throughput-sequencing data. Although a longer read is more likely to be uniquely mapped to the reference genome, a quantitative analysis of the influence of read lengths on mappability has been lacking. To address this question, we evaluate the <italic>k</italic>
-mer distribution of the human reference genome. The <italic>k</italic>
-mer frequency is determined for <italic>k</italic>
ranging from 20 bp to 1000 bp.</p>
</sec>
<sec><title>Results</title>
<p>We observe that the proportion of non-singletons <italic>k</italic>
-mers decreases slowly with increasing <italic>k</italic>
, and can be fitted by piecewise power-law functions with different exponents at different ranges of <italic>k</italic>
. A slower decay at greater values for <italic>k</italic>
indicates more limited gains in mappability for read lengths between 200 bp and 1000 bp. The frequency distributions of <italic>k</italic>
-mers exhibit long tails with a power-law-like trend, and rank frequency plots exhibit a concave Zipf’s curve. The most frequent 1000-mers comprise 172 regions, which include four large stretches on chromosomes 1 and X, containing genes of biomedical relevance. Comparison with other databases indicates that the 172 regions can be broadly classified into two types: those containing LINE transposable elements and those containing segmental duplications.</p>
</sec>
<sec><title>Conclusion</title>
<p>Read mappability as measured by the proportion of singletons increases steadily up to the length scale around 200 bp. When read length increases above 200 bp, smaller gains in mappability are expected. Moreover, the proportion of non-singletons decreases with read lengths much slower than linear. Even a read length of 1000 bp would not allow the unique alignment of reads for many coding regions of human genes. A mix of techniques will be needed for efficiently producing high-quality data that cover the complete human genome.</p>
</sec>
</div>
</front>
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{{Explor lien |wiki= Sante |area= MersV1 |flux= Main |étape= Exploration |type= RBID |clé= PMC:3927684 |texte= Diminishing return for increased Mappability with longer sequencing reads: implications of the k-mer distributions in the human genome }}
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HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:24386976" \ | HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \ | NlmPubMed2Wicri -a MersV1
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