Standardizing next-generation sequencing experiments and analysis methods.
TL;DR: A lack of consensus exists on how best to design and analyze next-generation sequencing (NGS) studies and how to compare these data to previous and future work, which means the main purpose of such studies is somehow getting lost in the process of experimental design.
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Abstract: To the Editor:
The past few years have seen the emergence of new strategies for high-throughput DNA sequencing that have invigorated life science research. Because of these technological advances, the available sequencing data continue to expand. Additionally, cost reductions have made access to sequences of entire genomes easier for established laboratories and even easier for small research groups. A lack of consensus exists, however, on how best to design and analyze next-generation sequencing (NGS) studies and how to compare these data to previous and future work. Comparing different sequencing platforms and analysis methods, and thus their interpretations, is becoming more complicated. The main purpose of such studies is somehow getting lost in the process of experimental design as biologists confront new territory with NGS work, which requires handling more complex and powerful statistical methods and produces large data sets. Every new tool or method is being compared with existing methods, and investigators are using statistical arguments to propose that the new methods are better. Kiezun et al. (1) have recently …
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Citations
Human germline and pan-cancer variomes and their distinct functional profiles
Yang Pan,Konstantinos Karagiannis,Haichen Zhang,Hayley Dingerdissen,Amirhossein Shamsaddini,Quan Wan,Vahan Simonyan,Raja Mazumder,Raja Mazumder +8 more
TL;DR: This study investigated the effect of nsSNVs on more than 17 common types of post-translational modification (PTM) sites, active sites and binding sites and found distinct patterns of site disruptions due to germline and somatic ns SNVs.
VCGDB: a dynamic genome database of the Chinese population
Yunchao Ling,Yunchao Ling,Zhong Jin,Mingming Su,Mingming Su,Jun Zhong,Jun Zhong,Yongbing Zhao,Yongbing Zhao,Jun Yu,Jiayan Wu,Jingfa Xiao +11 more
TL;DR: The Virtual Chinese Genome Database (VCGDB), a dynamic genome database of the Chinese population based on the whole genome sequencing data of 194 individuals, provides dynamic genomic information, which contains 35 million single nucleotide variations (SNVs), 0.5 million insertions/deletions (indels), and 29 million rare variations, together with genomic annotation information.
Next in line in next-generation sequencing: are we there yet?
TL;DR: Current trends in sequencing technology and relative to novel therapies are reviewed to answer the questions: will this technique be the missing link to scaffold data between genome sequencing methods, which currently contribute volumes of data but with nominal insight into therapies?
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VCGDB: a dynamic genome database of the
Yunchao Ling,Zhong Jin,Mingming Su,Jun Zhong,Yongbing Zhao,Jun Yu,Jiayan Wu,Jingfa Xiao +7 more
- 01 Jan 2014
TL;DR: The Virtual Chinese Genome Database (VCGDB), a dynamic genome database of the Chinese population based on the whole genome sequencing data of 194 individuals, provides dynamic genomic information, which contains 35 million single nucleotide variations (SNVs), 0.5 million insertions/deletions (indels), and 29 million rare variations, together with genomic annotation information.
The Dynamic Exome: acquired variants as individuals age
Jasmin H. Bavarva,Hongseok Tae,Lauren J. McIver,Enusha Karunasena,Harold R. Garner +4 more
- 16 Jun 2014
TL;DR: The results suggest that “age” is an important variable while analyzing an individual human genome to extract individual-specific clinically significant information necessary for personalized genomics.
References
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TL;DR: It is shown that de novo point mutations are overwhelmingly paternal in origin (4:1 bias) and positively correlated with paternal age, consistent with the modest increased risk for children of older fathers to develop ASD.
De novo mutations revealed by whole-exome sequencing are strongly associated with autism
Stephen Sanders,Michael T. Murtha,Abha R. Gupta,John D. Murdoch,Melanie J. Raubeson,A. Jeremy Willsey,A. Gulhan Ercan-Sencicek,Nicholas M. DiLullo,Neelroop N. Parikshak,Jason L. Stein,Michael F. Walker,Gordon T. Ober,Nicole A. Teran,Youeun Song,Paul El-Fishawy,Ryan C. Murtha,Murim Choi,John D. Overton,Robert D. Bjornson,Nicholas Carriero,Kyle A. Meyer,Kaya Bilguvar,Shrikant Mane,Nenad Sestan,Richard P. Lifton,Murat Gunel,Kathryn Roeder,Daniel H. Geschwind,Bernie Devlin,Matthew W. State +29 more
TL;DR: It is shown, using whole-exome sequencing of 928 individuals, including 200 phenotypically discordant sibling pairs, that highly disruptive (nonsense and splice-site) de novo mutations in brain-expressed genes are associated with autism spectrum disorders and carry large effects.
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Patterns and rates of exonic de novo mutations in autism spectrum disorders
Benjamin M. Neale,Yan Kou,Li Liu,Avi Ma'ayan,Kaitlin E. Samocha,Kaitlin E. Samocha,Aniko Sabo,Chiao-Feng Lin,Christine Stevens,Li-San Wang,Vladimir Makarov,Paz Polak,Paz Polak,Seungtai Yoon,Jared Maguire,Emily L. Crawford,Nicholas G. Campbell,Evan T. Geller,Otto Valladares,Chad M. Schafer,Han Liu,Tuo Zhao,Guiqing Cai,Jayon Lihm,Ruth Dannenfelser,Omar Jabado,Zuleyma Peralta,Uma Nagaswamy,Donna M. Muzny,Jeffrey G. Reid,Irene Newsham,Yuanqing Wu,Lora Lewis,Yi Han,Benjamin F. Voight,Benjamin F. Voight,Elaine T. Lim,Elaine T. Lim,Elizabeth J. Rossin,Elizabeth J. Rossin,Andrew Kirby,Andrew Kirby,Jason Flannick,Menachem Fromer,Menachem Fromer,Khalid Shakir,Timothy Fennell,Kiran V. Garimella,Eric Banks,Ryan Poplin,Stacey Gabriel,Mark A. DePristo,Jack R. Wimbish,Braden E. Boone,Shawn Levy,Catalina Betancur,Shamil R. Sunyaev,Shamil R. Sunyaev,Eric Boerwinkle,Eric Boerwinkle,Joseph D. Buxbaum,Edwin H. Cook,Bernie Devlin,Richard A. Gibbs,Kathryn Roeder,Gerard D. Schellenberg,James S. Sutcliffe,Mark J. Daly,Mark J. Daly +68 more
TL;DR: Results from de novo events and a large parallel case–control study provide strong evidence in favour of CHD8 and KATNAL2 as genuine autism risk factors and support polygenic models in which spontaneous coding mutations in any of a large number of genes increases risk by 5- to 20-fold.
Exome sequencing and the genetic basis of complex traits
Adam Kiezun,Kiran V. Garimella,Ron Do,Ron Do,Nathan O. Stitziel,Nathan O. Stitziel,Benjamin M. Neale,Benjamin M. Neale,Paul J. McLaren,Paul J. McLaren,Namrata Gupta,Pamela Sklar,Patrick F. Sullivan,Jennifer L. Moran,Christina M. Hultman,Paul Lichtenstein,Patrik K. E. Magnusson,Thomas Lehner,Yin Yao Shugart,Alkes L. Price,Alkes L. Price,Paul I.W. de Bakker,Paul I.W. de Bakker,Paul I.W. de Bakker,Shaun Purcell,Shamil R. Sunyaev,Shamil R. Sunyaev +26 more
TL;DR: Exome sequencing methods and their applications in studies to identify the genetic basis of human complex traits are presented and include analyses of the whole-exome sequences of 438 individuals from across several studies.