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Fosmid-based whole genome haplotyping of a HapMap trio child: evaluation of Single Individual Haplotyping techniques

Identifieur interne : 000409 ( Pmc/Curation ); précédent : 000408; suivant : 000410

Fosmid-based whole genome haplotyping of a HapMap trio child: evaluation of Single Individual Haplotyping techniques

Auteurs : Jorge Duitama [Allemagne, Belgique] ; Gayle K. Mcewen [Allemagne] ; Thomas Huebsch [Allemagne] ; Stefanie Palczewski [Allemagne] ; Sabrina Schulz [Allemagne] ; Kevin Verstrepen [Belgique] ; Eun-Kyung Suk [Allemagne] ; Margret R. Hoehe [Allemagne]

Source :

RBID : PMC:3299995

Abstract

Determining the underlying haplotypes of individual human genomes is an essential, but currently difficult, step toward a complete understanding of genome function. Fosmid pool-based next-generation sequencing allows genome-wide generation of 40-kb haploid DNA segments, which can be phased into contiguous molecular haplotypes computationally by Single Individual Haplotyping (SIH). Many SIH algorithms have been proposed, but the accuracy of such methods has been difficult to assess due to the lack of real benchmark data. To address this problem, we generated whole genome fosmid sequence data from a HapMap trio child, NA12878, for which reliable haplotypes have already been produced. We assembled haplotypes using eight algorithms for SIH and carried out direct comparisons of their accuracy, completeness and efficiency. Our comparisons indicate that fosmid-based haplotyping can deliver highly accurate results even at low coverage and that our SIH algorithm, ReFHap, is able to efficiently produce high-quality haplotypes. We expanded the haplotypes for NA12878 by combining the current haplotypes with our fosmid-based haplotypes, producing near-to-complete new gold-standard haplotypes containing almost 98% of heterozygous SNPs. This improvement includes notable fractions of disease-related and GWA SNPs. Integrated with other molecular biological data sets, this phase information will advance the emerging field of diploid genomics.


Url:
DOI: 10.1093/nar/gkr1042
PubMed: 22102577
PubMed Central: 3299995

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PMC:3299995

Le document en format XML

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<p>Determining the underlying haplotypes of individual human genomes is an essential, but currently difficult, step toward a complete understanding of genome function. Fosmid pool-based next-generation sequencing allows genome-wide generation of 40-kb haploid DNA segments, which can be phased into contiguous molecular haplotypes computationally by Single Individual Haplotyping (SIH). Many SIH algorithms have been proposed, but the accuracy of such methods has been difficult to assess due to the lack of real benchmark data. To address this problem, we generated whole genome fosmid sequence data from a HapMap trio child, NA12878, for which reliable haplotypes have already been produced. We assembled haplotypes using eight algorithms for SIH and carried out direct comparisons of their accuracy, completeness and efficiency. Our comparisons indicate that fosmid-based haplotyping can deliver highly accurate results even at low coverage and that our SIH algorithm, ReFHap, is able to efficiently produce high-quality haplotypes. We expanded the haplotypes for NA12878 by combining the current haplotypes with our fosmid-based haplotypes, producing near-to-complete new gold-standard haplotypes containing almost 98% of heterozygous SNPs. This improvement includes notable fractions of disease-related and GWA SNPs. Integrated with other molecular biological data sets, this phase information will advance the emerging field of diploid genomics.</p>
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</TEI>
<pmc article-type="research-article">
<pmc-dir>properties open_access</pmc-dir>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-ta">Nucleic Acids Res</journal-id>
<journal-id journal-id-type="publisher-id">nar</journal-id>
<journal-id journal-id-type="hwp">nar</journal-id>
<journal-title-group>
<journal-title>Nucleic Acids Research</journal-title>
</journal-title-group>
<issn pub-type="ppub">0305-1048</issn>
<issn pub-type="epub">1362-4962</issn>
<publisher>
<publisher-name>Oxford University Press</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">22102577</article-id>
<article-id pub-id-type="pmc">3299995</article-id>
<article-id pub-id-type="doi">10.1093/nar/gkr1042</article-id>
<article-id pub-id-type="publisher-id">gkr1042</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Genomics</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Fosmid-based whole genome haplotyping of a HapMap trio child: evaluation of Single Individual Haplotyping techniques</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Duitama</surname>
<given-names>Jorge</given-names>
</name>
<xref ref-type="aff" rid="gkr1042-AFF1">
<sup>1</sup>
</xref>
<xref ref-type="aff" rid="gkr1042-AFF1">
<sup>2</sup>
</xref>
<xref ref-type="corresp" rid="gkr1042-COR1">*</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>McEwen</surname>
<given-names>Gayle K.</given-names>
</name>
<xref ref-type="aff" rid="gkr1042-AFF1">
<sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Huebsch</surname>
<given-names>Thomas</given-names>
</name>
<xref ref-type="aff" rid="gkr1042-AFF1">
<sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Palczewski</surname>
<given-names>Stefanie</given-names>
</name>
<xref ref-type="aff" rid="gkr1042-AFF1">
<sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Schulz</surname>
<given-names>Sabrina</given-names>
</name>
<xref ref-type="aff" rid="gkr1042-AFF1">
<sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Verstrepen</surname>
<given-names>Kevin</given-names>
</name>
<xref ref-type="aff" rid="gkr1042-AFF1">
<sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Suk</surname>
<given-names>Eun-Kyung</given-names>
</name>
<xref ref-type="aff" rid="gkr1042-AFF1">
<sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Hoehe</surname>
<given-names>Margret R.</given-names>
</name>
<xref ref-type="aff" rid="gkr1042-AFF1">
<sup>1</sup>
</xref>
<xref ref-type="corresp" rid="gkr1042-COR1">*</xref>
</contrib>
</contrib-group>
<aff id="gkr1042-AFF1">
<sup>1</sup>
Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Ihnestr. 63-73, D-14195 Berlin, Germany,
<sup>2</sup>
VIB Laboratory of Systems Biology & Laboratory for Genetics and Genomics, Center of Microbial and Plant Genetics, K.U.Leuven, Gaston Geenslaan 1, B-3001 Leuven (Heverlee), Belgium</aff>
<author-notes>
<corresp id="gkr1042-COR1">*To whom correspondence should be addressed. Tel:
<phone>+49 30 8413 1468</phone>
; Fax:
<fax>+49 30 8413 1462</fax>
; Email:
<email>hoehe@molgen.mpg.de</email>
</corresp>
<corresp>Correspondence can also be addressed to Jorge Duitama. Tel:
<phone>+32 1675 1402</phone>
; Fax:
<fax>+32 1675 1391</fax>
; Email:
<email>Jorge.DuitamaCastellanos@biw.vib-kuleuven.be</email>
</corresp>
<fn>
<p>The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.</p>
</fn>
</author-notes>
<pmc-comment>For NAR both ppub and collection dates generated for PMC processing 1/27/05 beck</pmc-comment>
<pub-date pub-type="collection">
<month>3</month>
<year>2012</year>
</pub-date>
<pub-date pub-type="ppub">
<month>3</month>
<year>2012</year>
</pub-date>
<pub-date pub-type="epub">
<day>17</day>
<month>11</month>
<year>2011</year>
</pub-date>
<pub-date pub-type="pmc-release">
<day>17</day>
<month>11</month>
<year>2011</year>
</pub-date>
<pmc-comment> PMC Release delay is 0 months and 0 days and was based on the . </pmc-comment>
<volume>40</volume>
<issue>5</issue>
<fpage>2041</fpage>
<lpage>2053</lpage>
<history>
<date date-type="received">
<day>10</day>
<month>8</month>
<year>2011</year>
</date>
<date date-type="rev-recd">
<day>4</day>
<month>10</month>
<year>2011</year>
</date>
<date date-type="accepted">
<day>23</day>
<month>10</month>
<year>2011</year>
</date>
</history>
<permissions>
<copyright-statement>© The Author(s) 2011. Published by Oxford University Press.</copyright-statement>
<copyright-year>2011</copyright-year>
<license license-type="creative-commons" xlink:href="http://creativecommons.org/licenses/by-nc/3.0">
<license-p>
<pmc-comment>CREATIVE COMMONS</pmc-comment>
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (
<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by-nc/3.0">http://creativecommons.org/licenses/by-nc/3.0</ext-link>
), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
</license>
</permissions>
<abstract>
<p>Determining the underlying haplotypes of individual human genomes is an essential, but currently difficult, step toward a complete understanding of genome function. Fosmid pool-based next-generation sequencing allows genome-wide generation of 40-kb haploid DNA segments, which can be phased into contiguous molecular haplotypes computationally by Single Individual Haplotyping (SIH). Many SIH algorithms have been proposed, but the accuracy of such methods has been difficult to assess due to the lack of real benchmark data. To address this problem, we generated whole genome fosmid sequence data from a HapMap trio child, NA12878, for which reliable haplotypes have already been produced. We assembled haplotypes using eight algorithms for SIH and carried out direct comparisons of their accuracy, completeness and efficiency. Our comparisons indicate that fosmid-based haplotyping can deliver highly accurate results even at low coverage and that our SIH algorithm, ReFHap, is able to efficiently produce high-quality haplotypes. We expanded the haplotypes for NA12878 by combining the current haplotypes with our fosmid-based haplotypes, producing near-to-complete new gold-standard haplotypes containing almost 98% of heterozygous SNPs. This improvement includes notable fractions of disease-related and GWA SNPs. Integrated with other molecular biological data sets, this phase information will advance the emerging field of diploid genomics.</p>
</abstract>
<counts>
<page-count count="13"></page-count>
</counts>
</article-meta>
</front>
</pmc>
</record>

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