Technical Reports

  • Technical Report |

    PolyGembler, a method for grouping and ordering contigs into complete pseudomolecules by combining long-read sequencing and genotype information from an outbred mapping population, improves the accuracy for assembly of polyploidy plant genomes.

    • Chenxi Zhou
    • , Bode Olukolu
    • , Dorcus C. Gemenet
    • , Shan Wu
    • , Wolfgang Gruneberg
    • , Minh Duc Cao
    • , Zhangjun Fei
    • , Zhao-Bang Zeng
    • , Andrew W. George
    • , Awais Khan
    • , G. Craig Yencho
    •  & Lachlan J. M. Coin
  • Technical Report |

    STAAR is a powerful rare variant association test that incorporates variant functional categories and complementary functional annotations using a dynamic weighting scheme based on annotation principal components. STAAR accounts for population structure and relatedness and is scalable for analyzing large whole-genome sequencing studies.

    • Xihao Li
    • , Zilin Li
    • , Hufeng Zhou
    • , Sheila M. Gaynor
    • , Yaowu Liu
    • , Han Chen
    • , Ryan Sun
    • , Rounak Dey
    • , Donna K. Arnett
    • , Stella Aslibekyan
    • , Christie M. Ballantyne
    • , Lawrence F. Bielak
    • , John Blangero
    • , Eric Boerwinkle
    • , Donald W. Bowden
    • , Jai G. Broome
    • , Matthew P. Conomos
    • , Adolfo Correa
    • , L. Adrienne Cupples
    • , Joanne E. Curran
    • , Barry I. Freedman
    • , Xiuqing Guo
    • , George Hindy
    • , Marguerite R. Irvin
    • , Sharon L. R. Kardia
    • , Sekar Kathiresan
    • , Alyna T. Khan
    • , Charles L. Kooperberg
    • , Cathy C. Laurie
    • , X. Shirley Liu
    • , Michael C. Mahaney
    • , Ani W. Manichaikul
    • , Lisa W. Martin
    • , Rasika A. Mathias
    • , Stephen T. McGarvey
    • , Braxton D. Mitchell
    • , May E. Montasser
    • , Jill E. Moore
    • , Alanna C. Morrison
    • , Jeffrey R. O’Connell
    • , Nicholette D. Palmer
    • , Akhil Pampana
    • , Juan M. Peralta
    • , Patricia A. Peyser
    • , Bruce M. Psaty
    • , Susan Redline
    • , Kenneth M. Rice
    • , Stephen S. Rich
    • , Jennifer A. Smith
    • , Hemant K. Tiwari
    • , Michael Y. Tsai
    • , Ramachandran S. Vasan
    • , Fei Fei Wang
    • , Daniel E. Weeks
    • , Zhiping Weng
    • , James G. Wilson
    • , Lisa R. Yanek
    • , Namiko Abe
    • , Gonçalo R. Abecasis
    • , Francois Aguet
    • , Christine Albert
    • , Laura Almasy
    • , Alvaro Alonso
    • , Seth Ament
    • , Peter Anderson
    • , Pramod Anugu
    • , Deborah Applebaum-Bowden
    • , Kristin Ardlie
    • , Dan Arking
    • , Donna K. Arnett
    • , Allison Ashley-Koch
    • , Stella Aslibekyan
    • , Tim Assimes
    • , Paul Auer
    • , Dimitrios Avramopoulos
    • , John Barnard
    • , Kathleen Barnes
    • , R. Graham Barr
    • , Emily Barron-Casella
    • , Lucas Barwick
    • , Terri Beaty
    • , Gerald Beck
    • , Diane Becker
    • , Lewis Becker
    • , Rebecca Beer
    • , Amber Beitelshees
    • , Emelia Benjamin
    • , Takis Benos
    • , Marcos Bezerra
    • , Lawrence F. Bielak
    • , Joshua Bis
    • , Thomas Blackwell
    • , John Blangero
    • , Eric Boerwinkle
    • , Donald W. Bowden
    • , Russell Bowler
    • , Jennifer Brody
    • , Ulrich Broeckel
    • , Jai G. Broome
    • , Karen Bunting
    • , Esteban Burchard
    • , Carlos Bustamante
    • , Erin Buth
    • , Brian Cade
    • , Jonathan Cardwell
    • , Vincent Carey
    • , Cara Carty
    • , Richard Casaburi
    • , James Casella
    • , Peter Castaldi
    • , Mark Chaffin
    • , Christy Chang
    • , Yi-Cheng Chang
    • , Daniel Chasman
    • , Sameer Chavan
    • , Bo-Juen Chen
    • , Wei-Min Chen
    • , Yii-Der Ida Chen
    • , Michael Cho
    • , Seung Hoan Choi
    • , Lee-Ming Chuang
    • , Mina Chung
    • , Ren-Hua Chung
    • , Clary Clish
    • , Suzy Comhair
    • , Matthew P. Conomos
    • , Elaine Cornell
    • , Adolfo Correa
    • , Carolyn Crandall
    • , James Crapo
    • , L. Adrienne Cupples
    • , Joanne E. Curran
    • , Jeffrey Curtis
    • , Brian Custer
    • , Coleen Damcott
    • , Dawood Darbar
    • , Sayantan Das
    • , Sean David
    • , Colleen Davis
    • , Michelle Daya
    • , Mariza de Andrade
    • , Lisa de las Fuentes
    • , Michael DeBaun
    • , Ranjan Deka
    • , Dawn DeMeo
    • , Scott Devine
    • , Qing Duan
    • , Ravi Duggirala
    • , Jon Peter Durda
    • , Susan Dutcher
    • , Charles Eaton
    • , Lynette Ekunwe
    • , Adel El Boueiz
    • , Patrick Ellinor
    • , Leslie Emery
    • , Serpil Erzurum
    • , Charles Farber
    • , Tasha Fingerlin
    • , Matthew Flickinger
    • , Myriam Fornage
    • , Nora Franceschini
    • , Chris Frazar
    • , Mao Fu
    • , Stephanie M. Fullerton
    • , Lucinda Fulton
    • , Stacey Gabriel
    • , Weiniu Gan
    • , Shanshan Gao
    • , Yan Gao
    • , Margery Gass
    • , Bruce Gelb
    • , Xiaoqi (Priscilla) Geng
    • , Mark Geraci
    • , Soren Germer
    • , Robert Gerszten
    • , Auyon Ghosh
    • , Richard Gibbs
    • , Chris Gignoux
    • , Mark Gladwin
    • , David Glahn
    • , Stephanie Gogarten
    • , Da-Wei Gong
    • , Harald Goring
    • , Sharon Graw
    • , Daniel Grine
    • , C. Charles Gu
    • , Yue Guan
    • , Xiuqing Guo
    • , Namrata Gupta
    • , Jeff Haessler
    • , Michael Hall
    • , Daniel Harris
    • , Nicola L. Hawley
    • , Jiang He
    • , Susan Heckbert
    • , Ryan Hernandez
    • , David Herrington
    • , Craig Hersh
    • , Bertha Hidalgo
    • , James Hixson
    • , Brian Hobbs
    • , John Hokanson
    • , Elliott Hong
    • , Karin Hoth
    • , Chao (Agnes) Hsiung
    • , Yi-Jen Hung
    • , Haley Huston
    • , Chii Min Hwu
    • , Marguerite R. Irvin
    • , Rebecca Jackson
    • , Deepti Jain
    • , Cashell Jaquish
    • , Min A. Jhun
    • , Jill Johnsen
    • , Andrew Johnson
    • , Craig Johnson
    • , Rich Johnston
    • , Kimberly Jones
    • , Hyun Min Kang
    • , Robert Kaplan
    • , Sharon L. R. Kardia
    • , Sekar Kathiresan
    • , Shannon Kelly
    • , Eimear Kenny
    • , Michael Kessler
    • , Alyna T. Khan
    • , Wonji Kim
    • , Greg Kinney
    • , Barbara Konkle
    • , Charles L. Kooperberg
    • , Holly Kramer
    • , Christoph Lange
    • , Ethan Lange
    • , Leslie Lange
    • , Cathy C. Laurie
    • , Cecelia Laurie
    • , Meryl LeBoff
    • , Jiwon Lee
    • , Seunggeun Shawn Lee
    • , Wen-Jane Lee
    • , Jonathon LeFaive
    • , David Levine
    • , Dan Levy
    • , Joshua Lewis
    • , Xiaohui Li
    • , Yun Li
    • , Henry Lin
    • , Honghuang Lin
    • , Keng Han Lin
    • , Xihong Lin
    • , Simin Liu
    • , Yongmei Liu
    • , Yu Liu
    • , Ruth J. F. Loos
    • , Steven Lubitz
    • , Kathryn Lunetta
    • , James Luo
    • , Michael C. Mahaney
    • , Barry Make
    • , Ani W. Manichaikul
    • , JoAnn Manson
    • , Lauren Margolin
    • , Lisa W. Martin
    • , Susan Mathai
    • , Rasika A. Mathias
    • , Susanne May
    • , Patrick McArdle
    • , Merry-Lynn McDonald
    • , Sean McFarland
    • , Stephen T. McGarvey
    • , Daniel McGoldrick
    • , Caitlin McHugh
    • , Hao Mei
    • , Luisa Mestroni
    • , Deborah A. Meyers
    • , Julie Mikulla
    • , Nancy Min
    • , Mollie Minear
    • , Ryan L. Minster
    • , Braxton D. Mitchell
    • , Matt Moll
    • , May E. Montasser
    • , Courtney Montgomery
    • , Arden Moscati
    • , Solomon Musani
    • , Stanford Mwasongwe
    • , Josyf C. Mychaleckyj
    • , Girish Nadkarni
    • , Rakhi Naik
    • , Take Naseri
    • , Pradeep Natarajan
    • , Sergei Nekhai
    • , Sarah C. Nelson
    • , Bonnie Neltner
    • , Deborah Nickerson
    • , Kari North
    • , Jeffrey R. O’Connell
    • , Tim O’Connor
    • , Heather Ochs-Balcom
    • , David Paik
    • , Nicholette D. Palmer
    • , James Pankow
    • , George Papanicolaou
    • , Afshin Parsa
    • , Juan M. Peralta
    • , Marco Perez
    • , James Perry
    • , Ulrike Peters
    • , Patricia A. Peyser
    • , Lawrence S. Phillips
    • , Toni Pollin
    • , Wendy Post
    • , Julia Powers Becker
    • , Meher Preethi Boorgula
    • , Michael Preuss
    • , Bruce M. Psaty
    • , Pankaj Qasba
    • , Dandi Qiao
    • , Zhaohui Qin
    • , Nicholas Rafaels
    • , Laura Raffield
    • , Ramachandran S. Vasan
    • , D. C. Rao
    • , Laura Rasmussen-Torvik
    • , Aakrosh Ratan
    • , Susan Redline
    • , Robert Reed
    • , Elizabeth Regan
    • , Alex Reiner
    • , Muagututi‘a Sefuiva Reupena
    • , Kenneth M. Rice
    • , Stephen S. Rich
    • , Dan Roden
    • , Carolina Roselli
    • , Jerome I. Rotter
    • , Ingo Ruczinski
    • , Pamela Russell
    • , Sarah Ruuska
    • , Kathleen Ryan
    • , Ester Cerdeira Sabino
    • , Danish Saleheen
    • , Shabnam Salimi
    • , Steven Salzberg
    • , Kevin Sandow
    • , Vijay G. Sankaran
    • , Christopher Scheller
    • , Ellen Schmidt
    • , Karen Schwander
    • , David Schwartz
    • , Frank Sciurba
    • , Christine Seidman
    • , Jonathan Seidman
    • , Vivien Sheehan
    • , Stephanie L. Sherman
    • , Amol Shetty
    • , Aniket Shetty
    • , Wayne Hui-Heng Sheu
    • , M. Benjamin Shoemaker
    • , Brian Silver
    • , Edwin Silverman
    • , Jennifer A. Smith
    • , Josh Smith
    • , Nicholas Smith
    • , Tanja Smith
    • , Sylvia Smoller
    • , Beverly Snively
    • , Michael Snyder
    • , Tamar Sofer
    • , Nona Sotoodehnia
    • , Adrienne M. Stilp
    • , Garrett Storm
    • , Elizabeth Streeten
    • , Jessica Lasky Su
    • , Yun Ju Sung
    • , Jody Sylvia
    • , Adam Szpiro
    • , Carole Sztalryd
    • , Daniel Taliun
    • , Hua Tang
    • , Margaret Taub
    • , Kent D. Taylor
    • , Matthew Taylor
    • , Simeon Taylor
    • , Marilyn Telen
    • , Timothy A. Thornton
    • , Machiko Threlkeld
    • , Lesley Tinker
    • , David Tirschwell
    • , Sarah Tishkoff
    • , Hemant K. Tiwari
    • , Catherine Tong
    • , Russell Tracy
    • , Michael Y. Tsai
    • , Dhananjay Vaidya
    • , David Van Den Berg
    • , Peter VandeHaar
    • , Scott Vrieze
    • , Tarik Walker
    • , Robert Wallace
    • , Avram Walts
    • , Fei Fei Wang
    • , Heming Wang
    • , Karol Watson
    • , Daniel E. Weeks
    • , Bruce Weir
    • , Scott Weiss
    • , Lu-Chen Weng
    • , Jennifer Wessel
    • , Cristen J. Willer
    • , Kayleen Williams
    • , L. Keoki Williams
    • , Carla Wilson
    • , James G. Wilson
    • , Quenna Wong
    • , Joseph Wu
    • , Huichun Xu
    • , Lisa R. Yanek
    • , Ivana Yang
    • , Rongze Yang
    • , Norann Zaghloul
    • , Maryam Zekavat
    • , Yingze Zhang
    • , Snow Xueyan Zhao
    • , Wei Zhao
    • , Degui Zhi
    • , Xiang Zhou
    • , Xiaofeng Zhu
    • , Michael Zody
    • , Sebastian Zoellner
    • , Moustafa Abdalla
    • , Gonçalo R. Abecasis
    • , Donna K. Arnett
    • , Stella Aslibekyan
    • , Tim Assimes
    • , Elizabeth Atkinson
    • , Christie M. Ballantyne
    • , Amber Beitelshees
    • , Lawrence F. Bielak
    • , Joshua Bis
    • , Corneliu Bodea
    • , Eric Boerwinkle
    • , Donald W. Bowden
    • , Jennifer Brody
    • , Brian Cade
    • , Jenna Carlson
    • , I-Shou Chang
    • , Yii-Der Ida Chen
    • , Sung Chun
    • , Ren-Hua Chung
    • , Matthew P. Conomos
    • , Adolfo Correa
    • , L. Adrienne Cupples
    • , Coleen Damcott
    • , Paul de Vries
    • , Ron Do
    • , Amanda Elliott
    • , Mao Fu
    • , Andrea Ganna
    • , Da-Wei Gong
    • , Sarah Graham
    • , Mary Haas
    • , Bernhard Haring
    • , Jiang He
    • , Susan Heckbert
    • , Blanca Himes
    • , James Hixson
    • , Marguerite R. Irvin
    • , Deepti Jain
    • , Gail Jarvik
    • , Min A. Jhun
    • , Jicai Jiang
    • , Goo Jun
    • , Rita Kalyani
    • , Sharon L. R. Kardia
    • , Sekar Kathiresan
    • , Amit Khera
    • , Derek Klarin
    • , Charles L. Kooperberg
    • , Brian Kral
    • , Leslie Lange
    • , Cathy C. Laurie
    • , Cecelia Laurie
    • , Rozenn Lemaitre
    • , Zilin Li
    • , Xihao Li
    • , Xihong Lin
    • , Michael C. Mahaney
    • , Ani W. Manichaikul
    • , Lisa W. Martin
    • , Rasika A. Mathias
    • , Ravi Mathur
    • , Stephen T. McGarvey
    • , Caitlin McHugh
    • , John McLenithan
    • , Julie Mikulla
    • , Braxton D. Mitchell
    • , May E. Montasser
    • , Andrew Moran
    • , Alanna C. Morrison
    • , Tetsushi Nakao
    • , Pradeep Natarajan
    • , Deborah Nickerson
    • , Kari North
    • , Jeffrey R. O’Connell
    • , Christopher O’Donnell
    • , Nicholette D. Palmer
    • , Akhil Pampana
    • , Aniruddh Patel
    • , Gina M. Peloso
    • , James Perry
    • , Ulrike Peters
    • , Patricia A. Peyser
    • , James Pirruccello
    • , Toni Pollin
    • , Michael Preuss
    • , Bruce M. Psaty
    • , D. C. Rao
    • , Susan Redline
    • , Robert Reed
    • , Alex Reiner
    • , Stephen S. Rich
    • , Samantha Rosenthal
    • , Jerome I. Rotter
    • , Jenny Schoenberg
    • , Margaret Sunitha Selvaraj
    • , Wayne Hui-Heng Sheu
    • , Jennifer A. Smith
    • , Tamar Sofer
    • , Adrienne M. Stilp
    • , Shamil R. Sunyaev
    • , Ida Surakka
    • , Carole Sztalryd
    • , Hua Tang
    • , Kent D. Taylor
    • , Michael Y. Tsai
    • , Md Mesbah Uddin
    • , Sarah Urbut
    • , Marie Verbanck
    • , Ann Von Holle
    • , Heming Wang
    • , Fei Fei Wang
    • , Kerri Wiggins
    • , Cristen J. Willer
    • , James G. Wilson
    • , Brooke Wolford
    • , Huichun Xu
    • , Lisa R. Yanek
    • , Norann Zaghloul
    • , Maryam Zekavat
    • , Jingwen Zhang
    • , Benjamin M. Neale
    • , Shamil R. Sunyaev
    • , Gonçalo R. Abecasis
    • , Jerome I. Rotter
    • , Cristen J. Willer
    • , Gina M. Peloso
    • , Pradeep Natarajan
    •  & Xihong Lin
  • Technical Report |

    SAIGE-GENE is a scalable generalized mixed-model region-based association test that can analyze large datasets while accounting for sample relatedness and unbalanced case–control ratios for binary traits.

    • Wei Zhou
    • , Zhangchen Zhao
    • , Jonas B. Nielsen
    • , Lars G. Fritsche
    • , Jonathon LeFaive
    • , Sarah A. Gagliano Taliun
    • , Wenjian Bi
    • , Maiken E. Gabrielsen
    • , Mark J. Daly
    • , Benjamin M. Neale
    • , Kristian Hveem
    • , Goncalo R. Abecasis
    • , Cristen J. Willer
    •  & Seunggeun Lee
  • Technical Report |

    The authors present a high-throughput single-cell ChIP-seq method with coverage of up to 10,000 loci per cell. They identify diverse chromatin landscapes in breast cancer cells characterized by dynamic H3K27me3 levels.

    • Kevin Grosselin
    • , Adeline Durand
    • , Justine Marsolier
    • , Adeline Poitou
    • , Elisabetta Marangoni
    • , Fariba Nemati
    • , Ahmed Dahmani
    • , Sonia Lameiras
    • , Fabien Reyal
    • , Olivia Frenoy
    • , Yannick Pousse
    • , Marcel Reichen
    • , Adam Woolfe
    • , Colin Brenan
    • , Andrew D. Griffiths
    • , Céline Vallot
    •  & Annabelle Gérard
  • Technical Report |

    Signature Multivariate Analysis is a new computational tool that detects the mutational signature of homologous-recombination deficiency in clinical samples sequenced with targeted panels, enabling the identification of patients who are responsive to poly (ADP-ribose) polymerase inhibition therapy.

    • Doga C. Gulhan
    • , Jake June-Koo Lee
    • , Giorgio E. M. Melloni
    • , Isidro Cortés-Ciriano
    •  & Peter J. Park
  • Technical Report |

    Linked-read analysis is a method for analyzing single-cell DNA-sequencing data that accurately identifies somatic single-nucleotide variants by using read-level phasing with nearby germline variants, enabling the characterization of mutational signatures and estimation of somatic mutation rates in single cells.

    • Craig L. Bohrson
    • , Alison R. Barton
    • , Michael A. Lodato
    • , Rachel E. Rodin
    • , Lovelace J. Luquette
    • , Vinay V. Viswanadham
    • , Doga C. Gulhan
    • , Isidro Cortés-Ciriano
    • , Maxwell A. Sherman
    • , Minseok Kwon
    • , Michael E. Coulter
    • , Alon Galor
    • , Christopher A. Walsh
    •  & Peter J. Park
  • Technical Report |

    UTMOST (unified test for molecular signatures) is a method for cross-tissue gene expression imputation for transcriptome-wide association analyses. Cross-tissue TWAS using UTMOST identifies new candidate genes for late-onset Alzheimer’s disease.

    • Yiming Hu
    • , Mo Li
    • , Qiongshi Lu
    • , Haoyi Weng
    • , Jiawei Wang
    • , Seyedeh M. Zekavat
    • , Zhaolong Yu
    • , Boyang Li
    • , Jianlei Gu
    • , Sydney Muchnik
    • , Yu Shi
    • , Brian W. Kunkle
    • , Shubhabrata Mukherjee
    • , Pradeep Natarajan
    • , Adam Naj
    • , Amanda Kuzma
    • , Yi Zhao
    • , Paul K. Crane
    • , Hui Lu
    •  & Hongyu Zhao
  • Technical Report |

    GARFIELD is a new approach that classifies genomic features related to phenotypes on the basis of integrating GWAS signals with functional annotations. GARFIELD is used to characterize enrichment patterns for 29 traits integrated with ENCODE and Roadmap Epigenomics annotations.

    • Valentina Iotchkova
    • , Graham R. S. Ritchie
    • , Matthias Geihs
    • , Sandro Morganella
    • , Josine L. Min
    • , Klaudia Walter
    • , Nicholas John Timpson
    • , Ian Dunham
    • , Ewan Birney
    •  & Nicole Soranzo
  • Technical Report |

    Graph Genome Pipeline is a read-alignment and variant-calling pipeline based on graph genomes that offers improved read-mapping and variant-calling accuracy while achieving speed comparable to those of linear reference genome pipelines.

    • Goran Rakocevic
    • , Vladimir Semenyuk
    • , Wan-Ping Lee
    • , James Spencer
    • , John Browning
    • , Ivan J. Johnson
    • , Vladan Arsenijevic
    • , Jelena Nadj
    • , Kaushik Ghose
    • , Maria C. Suciu
    • , Sun-Gou Ji
    • , Gülfem Demir
    • , Lizao Li
    • , Berke Ç. Toptaş
    • , Alexey Dolgoborodov
    • , Björn Pollex
    • , Iosif Spulber
    • , Irina Glotova
    • , Péter Kómár
    • , Andrew L. Stachyra
    • , Yilong Li
    • , Milos Popovic
    • , Morten Källberg
    • , Amit Jain
    •  & Deniz Kural
  • Technical Report |

    StructLMM is a new method to identify genotype–environment interactions (G×E) that involve multiple exposures or environments. When applied to UK Biobank and eQTL data, StructLMM discovers new G×E signals.

    • Rachel Moore
    • , Francesco Paolo Casale
    • , Marc Jan Bonder
    • , Danilo Horta
    • , Bastiaan T. Heijmans
    • , Peter A. C.’t Hoen
    • , Joyce van Meurs
    • , Aaron Isaacs
    • , Rick Jansen
    • , Lude Franke
    • , Dorret I. Boomsma
    • , René Pool
    • , Jenny van Dongen
    • , Jouke J. Hottenga
    • , Marleen M. J. van Greevenbroek
    • , Coen D. A. Stehouwer
    • , Carla J. H. van der Kallen
    • , Casper G. Schalkwijk
    • , Cisca Wijmenga
    • , Alexandra Zhernakova
    • , Ettje F. Tigchelaar
    • , P. Eline Slagboom
    • , Marian Beekman
    • , Joris Deelen
    • , Diana van Heemst
    • , Jan H. Veldink
    • , Leonard H. van den Berg
    • , Cornelia M. van Duijn
    • , Bert A. Hofman
    • , André G. Uitterlinden
    • , P. Mila Jhamai
    • , Michael Verbiest
    • , H. Eka D. Suchiman
    • , Marijn Verkerk
    • , Ruud van der Breggen
    • , Jeroen van Rooij
    • , Nico Lakenberg
    • , Hailiang Mei
    • , Maarten van Iterson
    • , Michiel van Galen
    • , Jan Bot
    • , Peter van’t Hof
    • , Patrick Deelen
    • , Irene Nooren
    • , Matthijs Moed
    • , Martijn Vermaat
    • , Dasha V. Zhernakova
    • , René Luijk
    • , Marc Jan Bonder
    • , Freerk van Dijk
    • , Wibowo Arindrarto
    • , Szymon M. Kielbasa
    • , Morris A. Swertz
    • , Erik W. van Zwet
    • , Lude Franke
    • , Inês Barroso
    •  & Oliver Stegle
  • Technical Report |

    A machine learning approach for refinement of somatic variant calls automates this process and reduces bias stemming from inter-reviewer variability.

    • Benjamin J. Ainscough
    • , Erica K. Barnell
    • , Peter Ronning
    • , Katie M. Campbell
    • , Alex H. Wagner
    • , Todd A. Fehniger
    • , Gavin P. Dunn
    • , Ravindra Uppaluri
    • , Ramaswamy Govindan
    • , Thomas E. Rohan
    • , Malachi Griffith
    • , Elaine R. Mardis
    • , S. Joshua Swamidass
    •  & Obi L. Griffith
  • Technical Report |

    Tri-C is a new 3C approach to identify concurrent chromatin interactions at individual alleles. The authors observe specific higher-order structures involving simultaneous interactions between multiple enhancers and promoters, called regulatory hubs.

    • A. Marieke Oudelaar
    • , James O. J. Davies
    • , Lars L. P. Hanssen
    • , Jelena M. Telenius
    • , Ron Schwessinger
    • , Yu Liu
    • , Jill M. Brown
    • , Damien J. Downes
    • , Andrea M. Chiariello
    • , Simona Bianco
    • , Mario Nicodemi
    • , Veronica J. Buckle
    • , Job Dekker
    • , Douglas R. Higgs
    •  & Jim R. Hughes
  • Technical Report |

    BayesTyper is a new probabilistic genotyping algorithm that offers superior sensitivity and accuracy relative to existing methods by using exact alignment of read k-mers to a graph representation of the reference and candidate variants.

    • Jonas Andreas Sibbesen
    • , Lasse Maretty
    •  & Anders Krogh
  • Technical Report |

    LeafCutter is a new tool that identifies variable intron splicing events from RNA-seq data for analysis of complex alternative splicing. The method does not require transcript annotation and can be used to map splicing quantitative trait loci.

    • Yang I. Li
    • , David A. Knowles
    • , Jack Humphrey
    • , Alvaro N. Barbeira
    • , Scott P. Dickinson
    • , Hae Kyung Im
    •  & Jonathan K. Pritchard
  • Technical Report |

    Covariates for multiphenotype studies (CMS), a new approach for testing for associations from large-scale datasets, leverages genetic and environmental factors shared between correlated variables measured on the same samples. Applying CMS to real and simulated data demonstrates a large increase in power equivalent to that gained by doubling the sample size.

    • Hugues Aschard
    • , Vincent Guillemot
    • , Bjarni Vilhjalmsson
    • , Chirag J Patel
    • , David Skurnik
    • , Chun J Ye
    • , Brian Wolpin
    • , Peter Kraft
    •  & Noah Zaitlen
  • Technical Report |

    Graphtyper is a fast and scalable method for variant genotyping that aligns short-read sequence data to a pangenome. Graphtyper was able to accurately genotype 90 million sequence variants in the whole genomes of 28,000 Icelanders, including those in six HLA genes.

    • Hannes P Eggertsson
    • , Hakon Jonsson
    • , Snaedis Kristmundsdottir
    • , Eirikur Hjartarson
    • , Birte Kehr
    • , Gisli Masson
    • , Florian Zink
    • , Kristjan E Hjorleifsson
    • , Aslaug Jonasdottir
    • , Adalbjorg Jonasdottir
    • , Ingileif Jonsdottir
    • , Daniel F Gudbjartsson
    • , Pall Melsted
    • , Kari Stefansson
    •  & Bjarni V Halldorsson
  • Technical Report |

    Adam Siepel and colleagues report a new computational method, LINSIGHT, that combines evolutionary conservation and functional genomic information to predict the fitness consequences of noncoding mutations in the human genome. They use LINSIGHT to show that fitness consequences of enhancer mutations depend on tissue and cell type specificity and promoter constraints.

    • Yi-Fei Huang
    • , Brad Gulko
    •  & Adam Siepel
  • Technical Report |

    Kun Zhang and colleagues present a metric called methylation haplotype load (MHL) that quantifies methylation patterns within blocks of tightly linked CpG dinucleotides. They show that the MHL can distinguish samples from different human somatic tissues and that it can be used to improve detection of cancer-derived circulating DNA and identify its tissue of origin.

    • Shicheng Guo
    • , Dinh Diep
    • , Nongluk Plongthongkum
    • , Ho-Lim Fung
    • , Kang Zhang
    •  & Kun Zhang
  • Technical Report
    | Open Access

    Adam Phillippy, Curtis Van Tassell, Timothy Smith and colleagues present a new reference genome assembly for the domestic goat using a pipeline that improves contiguity of the assembly by more than 250-fold. The pipeline uses a combination of short- and long-read sequencing, optical mapping, and chromatin interaction mapping.

    • Derek M Bickhart
    • , Benjamin D Rosen
    • , Sergey Koren
    • , Brian L Sayre
    • , Alex R Hastie
    • , Saki Chan
    • , Joyce Lee
    • , Ernest T Lam
    • , Ivan Liachko
    • , Shawn T Sullivan
    • , Joshua N Burton
    • , Heather J Huson
    • , John C Nystrom
    • , Christy M Kelley
    • , Jana L Hutchison
    • , Yang Zhou
    • , Jiajie Sun
    • , Alessandra Crisà
    • , F Abel Ponce de León
    • , John C Schwartz
    • , John A Hammond
    • , Geoffrey C Waldbieser
    • , Steven G Schroeder
    • , George E Liu
    • , Maitreya J Dunham
    • , Jay Shendure
    • , Tad S Sonstegard
    • , Adam M Phillippy
    • , Curtis P Van Tassell
    •  & Timothy P L Smith
  • Technical Report |

    Stuart Orkin, Daniel Bauer and colleagues present DNA Striker, a computational tool to design variant-aware saturating-mutagenesis screens with multiple CRISPR-associated nucleases. They apply their methodology to the HBS1L-MYB intergenic region, which is associated with red-blood-cell traits, and identify putative regulatory elements that control MYB expression.

    • Matthew C Canver
    • , Samuel Lessard
    • , Luca Pinello
    • , Yuxuan Wu
    • , Yann Ilboudo
    • , Emily N Stern
    • , Austen J Needleman
    • , Frédéric Galactéros
    • , Carlo Brugnara
    • , Abdullah Kutlar
    • , Colin McKenzie
    • , Marvin Reid
    • , Diane D Chen
    • , Partha Pratim Das
    • , Mitchel A Cole
    • , Jing Zeng
    • , Ryo Kurita
    • , Yukio Nakamura
    • , Guo-Cheng Yuan
    • , Guillaume Lettre
    • , Daniel E Bauer
    •  & Stuart H Orkin
  • Technical Report |

    James Liley, John Todd and Chris Wallace present a statistical method for determining whether disease-associated variants have different effect sizes in phenotypically defined subgroups of disease cases. The test can be combined with existing methods to determine whether genetic heterogeneity is driven by population stratification or by different mechanisms of disease pathology.

    • James Liley
    • , John A Todd
    •  & Chris Wallace
  • Technical Report |

    Yun Song and colleagues present SMC++, a statistical method for population history inference capable of analyzing unphased whole genomes and sample sizes much larger than can be analyzed by current methods. The authors apply SMC++ to sequence data from human, Drosophila and finch populations.

    • Jonathan Terhorst
    • , John A Kamm
    •  & Yun S Song
  • Technical Report |

    John Storey, David Blei and colleagues present a method, TeraStructure, for estimating population structure from human genomic data sets on a scale not possible with current methods. TeraStructure is able to analyze data from the Human Genome Diversity Panel and the 1000 Genomes Project in less than three hours.

    • Prem Gopalan
    • , Wei Hao
    • , David M Blei
    •  & John D Storey
  • Technical Report |

    Gill Bejerano and colleagues present M-CAP, a classifier that estimates variant pathogenicity in clinical exome data sets. They show that M-CAP outperforms other existing methods at all thresholds and correctly dismisses 60% of rare missense variants of uncertain significance at 95% sensitivity.

    • Karthik A Jagadeesh
    • , Aaron M Wenger
    • , Mark J Berger
    • , Harendra Guturu
    • , Peter D Stenson
    • , David N Cooper
    • , Jonathan A Bernstein
    •  & Gill Bejerano
  • Technical Report |

    Po-Ru Loh, Alkes Price and colleagues present Eagle2, a reference-based phasing algorithm that allows for highly accurate and efficient phasing of genotypes across a broad range of cohort sizes. They demonstrate an approximately 10% improvement in accuracy and 20% improvement in speed compared to a competing method, SHAPEIT2.

    • Po-Ru Loh
    • , Petr Danecek
    • , Pier Francesco Palamara
    • , Christian Fuchsberger
    • , Yakir A Reshef
    • , Hilary K Finucane
    • , Sebastian Schoenherr
    • , Lukas Forer
    • , Shane McCarthy
    • , Goncalo R Abecasis
    • , Richard Durbin
    •  & Alkes L Price
  • Technical Report |

    Runjun Kumar, S. Joshua Swamidass and Ron Bose present an unsupervised parsimony-guided method, ParsSNP, for prioritizing candidate cancer driver mutations. They apply ParsSNP to a gastric cancer data set and predict potential driver mutations not detected by other methods, including truncations in known tumor-suppressor genes and previously confirmed drivers.

    • Runjun D Kumar
    • , S Joshua Swamidass
    •  & Ron Bose
  • Technical Report |

    Victoria Hore, Jonathan Marchini and colleagues present a method for multiple-tissue gene expression studies aimed at uncovering gene networks linked to genetic variation. They apply their method to RNA sequencing data from adipose, skin and lymphoblastoid cell lines and identify several biologically relevant gene networks with a genetic basis.

    • Victoria Hore
    • , Ana Viñuela
    • , Alfonso Buil
    • , Julian Knight
    • , Mark I McCarthy
    • , Kerrin Small
    •  & Jonathan Marchini
  • Technical Report |

    Richard Mott, Simon Myers and colleagues present a new imputation method, STITCH, which does not require genotyping arrays or high-quality reference panels. They use STITCH to accurately impute genotypes in both outbred laboratory mice and a sample human population directly from low-coverage (<2×) sequencing data.

    • Robert W Davies
    • , Jonathan Flint
    • , Simon Myers
    •  & Richard Mott
  • Technical Report |

    Po-Ru Loh, Pier Francesco Palamara and Alkes Price develop a new long-range phasing method, Eagle, that harnesses long, shared identical-by-descent tracts and can be applied to large outbred populations. They use Eagle to phase samples from the UK Biobank and find that it is faster and has better accuracy than existing methods.

    • Po-Ru Loh
    • , Pier Francesco Palamara
    •  & Alkes L Price
  • Technical Report |

    Jonathan Marchini and colleagues develop a new method for haplotype phasing, SHAPEIT3, capable of handling large data sets from biobanks containing >100,000 genotyped samples. They find that their method is fast and accurate, with a low switch error rate, and can be scaled to data sets from increasingly larger cohorts.

    • Jared O'Connell
    • , Kevin Sharp
    • , Nick Shrine
    • , Louise Wain
    • , Ian Hall
    • , Martin Tobin
    • , Jean-Francois Zagury
    • , Olivier Delaneau
    •  & Jonathan Marchini
  • Technical Report |

    Soumya Raychaudhuri, Buhm Han and colleagues present a statistical method to distinguish whether shared genetic risk variants among complex traits are driven by whole-group pleiotropy or a subset of individuals who constitute a genetically heterogeneous subgroup. They use the method to examine genetic sharing among autoimmune diseases and between major depressive disorder and schizophrenia and find that most genetic sharing cannot be explained by subgroup heterogeneity but that, in contrast, seronegative rheumatoid arthritis is a heterogeneous condition.

    • Buhm Han
    • , Jennie G Pouget
    • , Kamil Slowikowski
    • , Eli Stahl
    • , Cue Hyunkyu Lee
    • , Dorothee Diogo
    • , Xinli Hu
    • , Yu Rang Park
    • , Eunji Kim
    • , Peter K Gregersen
    • , Solbritt Rantapää Dahlqvist
    • , Jane Worthington
    • , Javier Martin
    • , Steve Eyre
    • , Lars Klareskog
    • , Tom Huizinga
    • , Wei-Min Chen
    • , Suna Onengut-Gumuscu
    • , Stephen S Rich
    • , Naomi R Wray
    •  & Soumya Raychaudhuri
  • Technical Report |

    Andy Dahl and colleagues present a method for imputing missing phenotype data in genetic studies with multiple correlated phenotypes where samples can have any level of relatedness. They apply their method to simulated and real data sets and show that it improves the sensitivity to detect association signals.

    • Andrew Dahl
    • , Valentina Iotchkova
    • , Amelie Baud
    • , Åsa Johansson
    • , Ulf Gyllensten
    • , Nicole Soranzo
    • , Richard Mott
    • , Andreas Kranis
    •  & Jonathan Marchini
  • Technical Report |

    Iuliana Ionita-Laza, Kenneth McCallum and colleagues developed an unsupervised statistical approach, Eigen, that integrates different functional annotations into a single measure of functional importance for coding and noncoding variants. Their meta-score can outperform the recently proposed CADD score and can be applied to fine-mapping studies.

    • Iuliana Ionita-Laza
    • , Kenneth McCallum
    • , Bin Xu
    •  & Joseph D Buxbaum
  • Technical Report |

    Natsuhiko Kumasaka, Andrew Knights and Daniel Gaffney develop a new statistical approach for association mapping that models genetic effects and accounts for biases in sequencing data in a single probabilistic framework. They apply this method to generate a map of chromatin accessibility QTLs and show how it can be used to fine-map regulatory variants and link distal regulatory elements with genes.

    • Natsuhiko Kumasaka
    • , Andrew J Knights
    •  & Daniel J Gaffney
  • Technical Report |

    Matthew Stephens and colleagues present a method for visualizing geographic patterns in genetic population structure. They apply this method to data from elephant, human and Arabidopsis thaliana populations and illustrate its potential to highlight barriers and corridors to gene flow.

    • Desislava Petkova
    • , John Novembre
    •  & Matthew Stephens
  • Technical Report |

    Kornelia Polyak, Franziska Michor and colleagues report a novel method, STAR-FISH, for combined in situ single-cell analysis of point mutations and copy number alterations in archived tissue samples. They apply STAR-FISH to clinically relevant PIK3CA mutations and HER2 amplifications and observe associations between intratumoral diversity and clinical outcome.

    • Michalina Janiszewska
    • , Lin Liu
    • , Vanessa Almendro
    • , Yanan Kuang
    • , Cloud Paweletz
    • , Rita A Sakr
    • , Britta Weigelt
    • , Ariella B Hanker
    • , Sarat Chandarlapaty
    • , Tari A King
    • , Jorge S Reis-Filho
    • , Carlos L Arteaga
    • , So Yeon Park
    • , Franziska Michor
    •  & Kornelia Polyak
  • Technical Report |

    Hae Kyung Im and colleagues report a method for predicting gene expression perturbations from genotype data after training on reference transcriptome data sets. Association of predicted gene expression with disease traits identifies known and new candidate disease genes.

    • Eric R Gamazon
    • , Heather E Wheeler
    • , Kaanan P Shah
    • , Sahar V Mozaffari
    • , Keston Aquino-Michaels
    • , Robert J Carroll
    • , Anne E Eyler
    • , Joshua C Denny
    • , Dan L Nicolae
    • , Nancy J Cox
    •  & Hae Kyung Im
  • Technical Report |

    Michael Beer and colleagues report a metric based on a regulatory region annotation method, gkm-SVM, and use this to predict the effects of regulatory variants from sequencing and DNase I–hypersensitive site data. They apply their method to autoimmune disease GWAS data and report several new predictions for causal SNPs.

    • Dongwon Lee
    • , David U Gorkin
    • , Maggie Baker
    • , Benjamin J Strober
    • , Alessandro L Asoni
    • , Andrew S McCallion
    •  & Michael A Beer