Effective detection of rare variants in pooled DNA samples using Cross-pool tailcurve analysis

Tejasvi S. Niranjan; Abby Adamczyk; Héctor C. Bravo; Margaret A. Taub; Sarah J. Wheelan; Rafael Irizarry; Tao Wang

doi:10.1186/gb-2011-12-9-r93

Effective detection of rare variants in pooled DNA samples using Cross-pool tailcurve analysis

Tejasvi S. Niranjan
, Abby Adamczyk
, Héctor C. Bravo
, Margaret A. Taub
, Sarah J. Wheelan
, Rafael Irizarry
, Tao Wang

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

Abstract

Sequencing targeted DNA regions in large samples is necessary to discover the full spectrum of rare variants. We report an effective Illumina sequencing strategy utilizing pooled samples with novel quality (Srfim) and filtering (SERVIC ⁴E) algorithms. We sequenced 24 exons in two cohorts of 480 samples each, identifying 47 coding variants, including 30 present once per cohort. Validation by Sanger sequencing revealed an excellent combination of sensitivity and specificity for variant detection in pooled samples of both cohorts as compared to publicly available algorithms.

Original language	English (US)
Article number	R93
Journal	Genome biology
Volume	12
Issue number	9
DOIs	https://doi.org/10.1186/gb-2011-12-9-r93
State	Published - Sep 28 2011

ASJC Scopus subject areas

Ecology, Evolution, Behavior and Systematics
Genetics
Cell Biology

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10.1186/gb-2011-12-9-r93

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@article{1a92f162205c4871ad5f917207eea4a0,

title = "Effective detection of rare variants in pooled DNA samples using Cross-pool tailcurve analysis",

abstract = "Sequencing targeted DNA regions in large samples is necessary to discover the full spectrum of rare variants. We report an effective Illumina sequencing strategy utilizing pooled samples with novel quality (Srfim) and filtering (SERVIC 4E) algorithms. We sequenced 24 exons in two cohorts of 480 samples each, identifying 47 coding variants, including 30 present once per cohort. Validation by Sanger sequencing revealed an excellent combination of sensitivity and specificity for variant detection in pooled samples of both cohorts as compared to publicly available algorithms.",

author = "Niranjan, \{Tejasvi S.\} and Abby Adamczyk and Bravo, \{H{\'e}ctor C.\} and Taub, \{Margaret A.\} and Wheelan, \{Sarah J.\} and Rafael Irizarry and Tao Wang",

note = "Funding Information: We thank Dr David Valle of Johns Hopkins University for critical reading of this manuscript, Autism Genetics Research Exchange (AGRE) and Greenwood Genetic Center (GGC) for DNA samples used in this study, and Dr Manuel Rivas of the Massachusetts Institute of Technology and the University of Oxford with assistance in running Syzygy. This work was supported in part by a pilot grant (\#2487) from Autism Speaks (to TW), a research grant from the Brain Science Institute at Johns Hopkins University, R01HD52680 from NICHD (to TW), and R01HG005220 from NHGRI (to RI). TSN is a student of the Predoctoral Training Program in Human Genetics at Johns Hopkins University.",

year = "2011",

month = sep,

day = "28",

doi = "10.1186/gb-2011-12-9-r93",

language = "English (US)",

volume = "12",

journal = "Genome biology",

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publisher = "BioMed Central",

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TY - JOUR

T1 - Effective detection of rare variants in pooled DNA samples using Cross-pool tailcurve analysis

AU - Niranjan, Tejasvi S.

AU - Adamczyk, Abby

AU - Bravo, Héctor C.

AU - Taub, Margaret A.

AU - Wheelan, Sarah J.

AU - Irizarry, Rafael

AU - Wang, Tao

N1 - Funding Information: We thank Dr David Valle of Johns Hopkins University for critical reading of this manuscript, Autism Genetics Research Exchange (AGRE) and Greenwood Genetic Center (GGC) for DNA samples used in this study, and Dr Manuel Rivas of the Massachusetts Institute of Technology and the University of Oxford with assistance in running Syzygy. This work was supported in part by a pilot grant (#2487) from Autism Speaks (to TW), a research grant from the Brain Science Institute at Johns Hopkins University, R01HD52680 from NICHD (to TW), and R01HG005220 from NHGRI (to RI). TSN is a student of the Predoctoral Training Program in Human Genetics at Johns Hopkins University.

PY - 2011/9/28

Y1 - 2011/9/28

N2 - Sequencing targeted DNA regions in large samples is necessary to discover the full spectrum of rare variants. We report an effective Illumina sequencing strategy utilizing pooled samples with novel quality (Srfim) and filtering (SERVIC 4E) algorithms. We sequenced 24 exons in two cohorts of 480 samples each, identifying 47 coding variants, including 30 present once per cohort. Validation by Sanger sequencing revealed an excellent combination of sensitivity and specificity for variant detection in pooled samples of both cohorts as compared to publicly available algorithms.

AB - Sequencing targeted DNA regions in large samples is necessary to discover the full spectrum of rare variants. We report an effective Illumina sequencing strategy utilizing pooled samples with novel quality (Srfim) and filtering (SERVIC 4E) algorithms. We sequenced 24 exons in two cohorts of 480 samples each, identifying 47 coding variants, including 30 present once per cohort. Validation by Sanger sequencing revealed an excellent combination of sensitivity and specificity for variant detection in pooled samples of both cohorts as compared to publicly available algorithms.

UR - https://www.scopus.com/pages/publications/80052868508

UR - https://www.scopus.com/pages/publications/80052868508#tab=citedBy

U2 - 10.1186/gb-2011-12-9-r93

DO - 10.1186/gb-2011-12-9-r93

M3 - Article

C2 - 21955804

AN - SCOPUS:80052868508

SN - 1474-7596

VL - 12

JO - Genome biology

JF - Genome biology

IS - 9

M1 - R93

ER -

Effective detection of rare variants in pooled DNA samples using Cross-pool tailcurve analysis

Abstract

ASJC Scopus subject areas

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