Benchmarking challenging small variants with linked and long reads.
Benchmarking challenging small variants with linked and long reads.
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DOI：
10.1016/j.xgen.2022.100128
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发表时间：
2022-05
期刊：
影响因子：
--
通讯作者：
Zook, Justin M.
中科院分区：
文献类型：
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作者：
Wagner, Justin;Olson, Nathan D.;Harris, Lindsay;Khan, Ziad;Farek, Jesse;Mahmoud, Medhat;Stankovic, Ana;Kovacevic, Vladimir;Yoo, Byunggil;Miller, Neil;Rosenfeld, Jeffrey A.;Ni, Bohan;Zarate, Samantha;Kirsche, Melanie;Aganezov, Sergey;Schatz, Michael C.;Narzisi, Giuseppe;Byrska-Bishop, Marta;Clarke, Wayne;Evani, Uday S.;Markello, Charles;Shafin, Kishwar;Zhou, Xin;Sidow, Arend;Bansal, Vikas;Ebert, Peter;Marschall, Tobias;Lansdorp, Peter;Hanlon, Vincent;Mattsson, Carl-Adam;Barrio, Alvaro Martinez;Fiddes, Ian T.;Xiao, Chunlin;Fungtammasan, Arkarachai;Chin, Chen-Shan;Wenger, Aaron M.;Rowell, William J.;Sedlazeck, Fritz J.;Carroll, Andrew;Salit, Marc;Zook, Justin M.
Genome in a Bottle基准被广泛用于帮助验证临床测序管道和开发变异识别和测序方法。在这里，我们使用准确的连接和长读段来扩展7个样本中的基准，以包括难以映射的区域和对短读段具有挑战性的片段重复。这些基准增加了超过300，000个SNV和50，000个插入或缺失（indels），并包括16%的外显子变异，其中许多是以前未涵盖的具有挑战性的临床相关基因，如PMS2。对于HG002，我们包括了92%的常染色体GRCh38组装，同时排除了对基准小变异有问题的区域，例如拷贝数变异，这些变异不应该出现在以前的版本中，其中包括85%的GRCh38。相对于我们之前的基准，它在短读变体调用集中识别出8倍以上的假阴性。我们证明，该基准可靠地识别跨技术的假阳性和假阴性，从而实现持续的方法开发。瓶内基因组联盟提出了一个扩展的7个基因组的基准长和连接的读取将基准扩展到对短读取具有挑战性的区域扩展的区域包括具有挑战性的医学相关基因，如PMS 2这使得新技术和生物信息学方法的开发成为可能类似于放置看起来相似的拼图，将序列映射到看起来相似的基因组区域是具有挑战性的。瓦格纳等人描述了一种新的瓶内基因组资源，用于在更具有挑战性的基因组区域中对人类基因组测序的准确性进行基准测试。
Genome in a Bottle benchmarks are widely used to help validate clinical sequencing pipelines and develop variant calling and sequencing methods. Here we use accurate linked and long reads to expand benchmarks in 7 samples to include difficult-to-map regions and segmental duplications that are challenging for short reads. These benchmarks add more than 300,000 SNVs and 50,000 insertions or deletions (indels) and include 16% more exonic variants, many in challenging, clinically relevant genes not covered previously, such as PMS2. For HG002, we include 92% of the autosomal GRCh38 assembly while excluding regions problematic for benchmarking small variants, such as copy number variants, that should not have been in the previous version, which included 85% of GRCh38. It identifies eight times more false negatives in a short read variant call set relative to our previous benchmark. We demonstrate that this benchmark reliably identifies false positives and false negatives across technologies, enabling ongoing methods development. The Genome in a Bottle Consortium presents an expanded benchmark for 7 genomes Long and linked reads expanded the benchmark to regions challenging for short reads The expanded regions include challenging medically relevant genes like PMS2 This enables development of new technologies and bioinformatics methods Analogous to placing puzzle pieces that look similar, mapping sequences to regions of the genome that look similar is challenging. Wagner et al. describe a new Genome in a Bottle Consortium resource for benchmarking accuracy of human genome sequencing in more challenging regions of the genome.
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影响因子：
14.9
作者：
Howe KL;Achuthan P;Allen J;Allen J;Alvarez-Jarreta J;Amode MR;Armean IM;Azov AG;Bennett R;Bhai J;Billis K;Boddu S;Charkhchi M;Cummins C;Da Rin Fioretto L;Davidson C;Dodiya K;El Houdaigui B;Fatima R;Gall A;Garcia Giron C;Grego T;Guijarro-Clarke C;Haggerty L;Hemrom A;Hourlier T;Izuogu OG;Juettemann T;Kaikala V;Kay M;Lavidas I;Le T;Lemos D;Gonzalez Martinez J;Marugán JC;Maurel T;McMahon AC;Mohanan S;Moore B;Muffato M;Oheh DN;Paraschas D;Parker A;Parton A;Prosovetskaia I;Sakthivel MP;Salam AIA;Schmitt BM;Schuilenburg H;Sheppard D;Steed E;Szpak M;Szuba M;Taylor K;Thormann A;Threadgold G;Walts B;Winterbottom A;Chakiachvili M;Chaubal A;De Silva N;Flint B;Frankish A;Hunt SE;IIsley GR;Langridge N;Loveland JE;Martin FJ;Mudge JM;Morales J;Perry E;Ruffier M;Tate J;Thybert D;Trevanion SJ;Cunningham F;Yates AD;Zerbino DR;Flicek P
通讯作者：
Flicek P
影响因子：
7
作者：
Miga KH;Newton Y;Jain M;Altemose N;Willard HF;Kent WJ
通讯作者：
Kent WJ
影响因子：
48
作者：
Cheng H;Concepcion GT;Feng X;Zhang H;Li H
通讯作者：
Li H
影响因子：
1.7
作者：
Patterson, Murray;Marschall, Tobias;Schonhuth, Alexander
通讯作者：
Schonhuth, Alexander
影响因子：
7
作者：
Eberle, Michael A.;Fritzilas, Epameinondas;Bentley, David R.
通讯作者：
Bentley, David R.