Variant Calling: Methods and Protocols

352 Pages·2022·8.149 MB·English

by  Charlotte Ng, Salvatore Piscuoglio

Methods in
Molecular Biology 2493
Charlotte K. Y. Ng
Salvatore Piscuoglio Editors
Variant Calling
Methods and Protocols
M M B
ETHODS IN OLECULAR IO LO GY
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Variant Calling
Methods and Protocols
Edited by
Charlotte K. Y. Ng
Department for BioMedical Research, University of Bern, Bern, Switzerland
Salvatore Piscuoglio
Department of Biomedicine, University of Basel, Basel, Switzerland
Editors
CharlotteK.Y.Ng SalvatorePiscuoglio
DepartmentforBioMedicalResearch DepartmentofBiomedicine
UniversityofBern UniversityofBasel
Bern,Switzerland Basel,Switzerland
ISSN1064-3745 ISSN1940-6029 (electronic)
MethodsinMolecularBiology
ISBN978-1-0716-2292-6 ISBN978-1-0716-2293-3 (eBook)
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Preface
Genetic diversity is fundamental to species adaptability and survival. The identification of
sequencevariationsprovidesinsights notonly intogeneticdiversitybut alsotothe genetic
component of diseases and phenotypes. The advances of next-generation sequencing over
the past two decades have offered the opportunity to comprehensively screen and detect
various types of variants in large populations. While the Human Genome Project took
13 years to complete, now entire genomes can be screened for genetic variations at single
base-pair resolution in a matter of days. The identification of variants in the nearly half-
millionsequencedspecieshasenabledsignificantadvancesinmanyfacets,frommedicineto
agriculture to industrial processes. The number of known variants will only continue to
increaseexponentiallywiththeEarthBioGenomeProjectaimingtosequenceandannotate
~1.5millionknowneukaryoticspeciesby2028.
This book was compiled in the midst of one of the great challenges in modern medi-
cine—theSARS-CoV-2pandemic.Beingabletorapidlysequencethepathogenandtraceits
variants as they spread across the world has been critical to pandemic response planning
aimingtocontainviralspread.Whiletheinitialvaccinesdevelopedatbreakneckspeedhave
proveneffective,theidentificationofnovelvariantsthatcouldcompromisetheirpotencyis
critical to the further development of vaccines. Next-generation sequencing and variant
detection,togetherwithotherpandemicresponsemeasures,haveundoubtedlysavedmany,
manylives.
The evolution of next-generation sequencing has necessitated the continual develop-
mentofalgorithmstoaddressspecificquestionsandtoovercomecomputationalchallenges.
The many types of sequencing protocols and technologies enable the discovery of many
different types of variants, each requiring specialist algorithms to accurately model the
underlying statistical properties. In this volume, we cover a diverse range of methods
relevanttovariantcalling.Inthefirstpart,Chapters1–11covergeneralmethodsforvariant
calling,withChapters1–5coveringapproachestocalling“classical”variants—singlenucle-
otide substitutions, insertions, and deletions—and Chapters 6–11 describing methods for
the identification of other, but no less biologically relevant, variant types—copy number
variants,structuralvariants,somaticmitochondrialvariants,andsplicevariants.Thesecond
part covers variant calling in specialized data types and use cases. Chapters 12–14 describe
threeapproaches to variant callingin specializeddatatypes—IonTorrent sequencingdata,
RNA-seqdata,andUMI-taggedpaired-endsequencingdata.Chapters15and16describe
alignment-freegenotypingandSNPcalling.Chapters17and18describesinglenucleotide
and copy number variant detection in single-cell DNA sequencing data. The third part
coverstopicsrelevantandimportanttovariantcalling,withChapters19and20dedicatedto
variant annotation—critical to biological interpretation—and Chapter 21 devoted to pre-
analytical quality control to ensure successful variant calling. The chapters should be of
interest to bioinformatics students and researchers alike looking to broaden and deepen
theirknowledgeonvariantcalling.
v
vi Preface
We would like to thank the authors for sharing their methods. We thank Springer
Nature and Series Editor Prof. John M Walker for giving us the opportunity to compile
thiscollectionandfor theirsupportthroughouttheprocess.
Bern,Switzerland CharlotteK.Y.Ng
Basel,Switzerland SalvatorePiscuoglio
Contents
Preface ..................................................................... v
Contributors................................................................. ix
1 DataProcessingandGermlineVariantCalling
withtheSentieonPipeline ............................................... 1
RafaelAldanaandDonaldFreed
2 MuSE:ANovelApproachtoMutationCalling
withSample-SpecificErrorModeling...................................... 21
ShuangxiJi,MatthewD.Montierth,andWenyiWang
3 Octopus:GenotypingandHaplotypinginDiverse
ExperimentalDesigns ................................................... 29
DanielP.Cooke
4 AccurateEnsemblePredictionofSomaticMutations
withSMuRF2 .......................................................... 53
WeitaiHuang,NgakLengSim,andAndersJ.Skanderup
5 DetectingMediumandLargeInsertionsandDeletions
withtransIndel ......................................................... 67
Ting-YouWangandRendongYang
6 DECoN:ADetectionandVisualizationToolforExonic
CopyNumberVariants .................................................. 77
AnnaFowler
7 FACETS:FractionandAllele-SpecificCopyNumberEstimates
fromTumorSequencing................................................. 89
ArshiArora,RonglaiShen,andVenkatramanE.Seshan
8 Meerkat:AnAlgorithmtoReliablyIdentifyStructural
VariationsandPredictTheirFormingMechanisms.......................... 107
LixingYang
9 StructuralVariantDetectionfromLong-ReadSequencing
DatawithcuteSV ....................................................... 137
TaoJiang,ShiqiLiu,ShuqiCao,andYadongWang
10 IdentifyingSomaticMitochondrialDNAMutations ........................ 153
JisongAn,KyoungIlMin,andYoungSeokJu
11 Identification,Quantification,andTestingofAlternative
SplicingEventsfromRNA-SeqDataUsingSplAdder ....................... 167
PhilippMarkolin,GunnarRa€tsch,andAndre´Kahles
12 PipeIT2:SomaticVariantCallingWorkflowforIon
TorrentSequencingData................................................ 195
AndreaGarofoli,De´sire´eSchnidrig,andCharlotteK.Y.Ng
13 VariantCallingfromRNA-seqDataUsingtheGATKJoint
GenotypingWorkflow................................................... 205
Jean-SimonBrouardandNathalieBissonnette
vii
viii Contents
14 UMI-Varcal:ALow-FrequencyVariantCaller forUMI-Tagged
Paired-EndSequencingData............................................. 235
VincentSater,Pierre-JulienViailly,ThierryLecroq,
E´lisePrieur-Gaston,E´lodieBohers,MathieuViennot,
PhilippeRuminy,He´le`neDauchel,PierreVera,andFabriceJardin
15 Alignment-FreeGenotypingofKnownVariationswithMALVA.............. 247
GiuliaBernardini,LucaDenti,andMarcoPrevitali
16 Kmer2SNP:Reference-FreeHeterozygousSNPCalling
Usingk-merFrequencyDistributions ..................................... 257
YanboLi,HardipPatel,andYuLin
17 SomaticSingle-NucleotideVariantCallingfromSingle-Cell
DNASequencingDataUsingSCAN-SNV................................. 267
SajedehBahonarandHesamMontazeri
18 CopyNumberVariationDetectionbySingle-CellDNA
SequencingwithSCOPE ................................................ 279
RujinWangandYuchaoJiang
19 VariantAnnotationandFunctionalPrediction:SnpEff ...................... 289
PabloCingolani
20 AnnotatingCancer-RelatedVariantsatProtein–Protein
InterfacewithStructure-PPi.............................................. 315
MiguelVazquezandTirsoPons
21 PreanalyticalVariablesandSampleQualityControlforClinical
VariantAnalysis......................................................... 331
IlariaAlborelliandPhilipM.Jermann
Index ...................................................................... 353
Contributors
ILARIAALBORELLI • InstituteofMedicalGeneticsandPathology,UniversityHospitalBasel,
Basel,Switzerland
RAFAELALDANA • Sentieon®Inc.,SanJose,CA,USA
JISONGAN • GraduateSchoolofMedicalScienceandEngineering(GSMSE),Korea
AdvancedInstituteofScienceandTechnology(KAIST),Daejeon,RepublicofKorea
ARSHIARORA • DepartmentofEpidemiology&Biostatistics,MemorialSloanKettering
CancerCenter,NewYork,NY,USA
SAJEDEHBAHONAR • DepartmentofBioinformatics,InstituteofBiochemistryandBiophysics
(IBB),UniversityofTehran,Tehran,Iran
GIULIABERNARDINI • CentrumWiskunde&Informatica,Amsterdam,TheNetherlands
NATHALIEBISSONNETTE • AgricultureandAgri-FoodCanada,Sherbrooke,QC,Canada
E´LODIE BOHERS • DepartmentofPathology,CentreHenriBecquerel,Rouen,France;
INSERMU1245,UniversityofNormandieUNIROUEN,Rouen,France
JEAN-SIMONBROUARD • AgricultureandAgri-FoodCanada,Sherbrooke,QC,Canada
SHUQICAO • HarbinInstituteofTechnology,Harbin,Heilongjiang,China
PABLO CINGOLANI • AstraZeneca,OncologyR&D,Arlington,MA,USA
DANIELP.COOKE • MRCWeatherallInstituteofMolecularMedicine,UniversityofOxford,
Oxford,UK
HE´LE`NEDAUCHEL • NormandieUniv,UNIROUEN,LITISEA4108,Rouen,France
LUCA DENTI • DepartmentofComputationalBiology,C3BIUSR3756CNRS,Institut
Pasteur,Paris,France
ANNAFOWLER • DepartmentofHealthDataScience,InstituteofPopulationHealth,
UniversityofLiverpool,Liverpool,UK
DONALD FREED • Sentieon®Inc.,SanJose,CA,USA
ANDREAGAROFOLI • InstituteofMedicalGeneticsandPathology,UniversityHospitalBasel,
Basel,Switzerland
WEITAIHUANG • LaboratoryofComputationalCancerGenomics,GenomeInstituteof
Singapore,A*STAR(AgencyforScience,TechnologyandResearch),Singapore,Singapore
FABRICEJARDIN • DepartmentofPathology,CentreHenriBecquerel,Rouen,France;
INSERMU1245,UniversityofNormandieUNIROUEN,Rouen,France
PHILIPM.JERMANN • InstituteofMedicalGeneticsandPathology,UniversityHospitalBasel,
Basel,Switzerland
SHUANGXIJI • DepartmentofBioinformaticsandComputationalBiology,TheUniversityof
TexasMDAndersonCancerCenter,Houston,TX,USA
TAOJIANG • HarbinInstituteofTechnology,Harbin,Heilongjiang,China
YUCHAOJIANG • DepartmentofBiostatistics,GillingsSchoolofGlobalPublicHealth,
UniversityofNorthCarolina,ChapelHill,NC,USA;DepartmentofGenetics,Schoolof
Medicine,UniversityofNorthCarolina,ChapelHill,NC,USA;Lineberger
ComprehensiveCancerCenter,UniversityofNorthCarolina,ChapelHill,NC,USA
YOUNGSEOKJU • GraduateSchoolofMedicalScienceandEngineering(GSMSE),Korea
AdvancedInstituteofScienceandTechnology(KAIST),Daejeon,RepublicofKorea
ix