PMID- 30384854
OWN - NLM
STAT- MEDLINE
DCOM- 20190211
LR  - 20221207
IS  - 1471-2164 (Electronic)
IS  - 1471-2164 (Linking)
VI  - 19
IP  - 1
DP  - 2018 Nov 1
TI  - ALPHLARD: a Bayesian method for analyzing HLA genes from whole genome sequence 
      data.
PG  - 790
LID - 10.1186/s12864-018-5169-9 [doi]
LID - 790
AB  - BACKGROUND: Although human leukocyte antigen (HLA) genotyping based on amplicon, 
      whole exome sequence (WES), and RNA sequence data has been achieved in recent 
      years, accurate genotyping from whole genome sequence (WGS) data remains a 
      challenge due to the low depth. Furthermore, there is no method to identify the 
      sequences of unknown HLA types not registered in HLA databases. RESULTS: We 
      developed a Bayesian model, called ALPHLARD, that collects reads potentially 
      generated from HLA genes and accurately determines a pair of HLA types for each 
      of HLA-A, -B, -C, -DPA1, -DPB1, -DQA1, -DQB1, and -DRB1 genes at 3rd field 
      resolution. Furthermore, ALPHLARD can detect rare germline variants not stored in 
      HLA databases and call somatic mutations from paired normal and tumor sequence 
      data. We illustrate the capability of ALPHLARD using 253 WES data and 25 WGS data 
      from Illumina platforms. By comparing the results of HLA genotyping from SBT and 
      amplicon sequencing methods, ALPHLARD achieved 98.8% for WES data and 98.5% for 
      WGS data at 2nd field resolution. We also detected three somatic point mutations 
      and one case of loss of heterozygosity in the HLA genes from the WGS data. 
      CONCLUSIONS: ALPHLARD showed good performance for HLA genotyping even from 
      low-coverage data. It also has a potential to detect rare germline variants and 
      somatic mutations in HLA genes. It would help to fill in the current gaps in HLA 
      reference databases and unveil the immunological significance of somatic 
      mutations identified in HLA genes.
FAU - Hayashi, Shuto
AU  - Hayashi S
AD  - Human Genome Center, The Institute of Medical Science, The University of Tokyo, 
      4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
FAU - Yamaguchi, Rui
AU  - Yamaguchi R
AD  - Human Genome Center, The Institute of Medical Science, The University of Tokyo, 
      4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
FAU - Mizuno, Shinichi
AU  - Mizuno S
AD  - Center for Advanced Medical Innovation, Kyushu University, 3-1-1 Maidashi, 
      Higashi-ku, Fukuoka, 812-8582, Japan.
FAU - Komura, Mitsuhiro
AU  - Komura M
AD  - Human Genome Center, The Institute of Medical Science, The University of Tokyo, 
      4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
FAU - Miyano, Satoru
AU  - Miyano S
AD  - Human Genome Center, The Institute of Medical Science, The University of Tokyo, 
      4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
FAU - Nakagawa, Hidewaki
AU  - Nakagawa H
AD  - RIKEN Center for Integrative Medical Sciences, 4-6-1 Shirokanedai, Minato-ku, 
      Tokyo, 108-8639, Japan.
FAU - Imoto, Seiya
AU  - Imoto S
AUID- ORCID: 0000-0002-2989-308X
AD  - Health Intelligence Center, The Institute of Medical Science, The University of 
      Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan. 
      imoto@ims.u-tokyo.ac.jp.
LA  - eng
GR  - 15H02775/Japan Society for the Promotion of Science/
GR  - 15H05912/Japan Society for the Promotion of Science/
PT  - Journal Article
DEP - 20181101
PL  - England
TA  - BMC Genomics
JT  - BMC genomics
JID - 100965258
RN  - 0 (HLA Antigens)
SB  - IM
MH  - Algorithms
MH  - Alleles
MH  - *Bayes Theorem
MH  - Computational Biology/*methods
MH  - Databases, Genetic
MH  - *Genome, Human
MH  - Genomics/*methods
MH  - Genotype
MH  - HLA Antigens/*genetics
MH  - Humans
MH  - Mutation
MH  - Exome Sequencing
MH  - *Whole Genome Sequencing
PMC - PMC6211482
OTO - NOTNLM
OT  - Bayesian hierarchical model
OT  - Cancer immunogenomics
OT  - HLA genotyping
OT  - Markov chain Monte Carlo
OT  - Next generation sequencing
OT  - Whole exome sequencing
OT  - Whole genome sequencing
COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: All of the human subjects agreed with 
      informed consent to participate in the study following ICGC guidelines [27]. IRBs 
      at RIKEN and the associated hospitals participating in this study approved this 
      work. CONSENT FOR PUBLICATION: Not applicable. COMPETING INTERESTS: The authors 
      declare that they have no competing interests. PUBLISHER'S NOTE: Springer Nature 
      remains neutral with regard to jurisdictional claims in published maps and 
      institutional affiliations.
EDAT- 2018/11/06 06:00
MHDA- 2019/02/12 06:00
PMCR- 2018/11/01
CRDT- 2018/11/03 06:00
PHST- 2018/05/17 00:00 [received]
PHST- 2018/10/15 00:00 [accepted]
PHST- 2018/11/03 06:00 [entrez]
PHST- 2018/11/06 06:00 [pubmed]
PHST- 2019/02/12 06:00 [medline]
PHST- 2018/11/01 00:00 [pmc-release]
AID - 10.1186/s12864-018-5169-9 [pii]
AID - 5169 [pii]
AID - 10.1186/s12864-018-5169-9 [doi]
PST - epublish
SO  - BMC Genomics. 2018 Nov 1;19(1):790. doi: 10.1186/s12864-018-5169-9.