PMID- 35238330
OWN - NLM
STAT- MEDLINE
DCOM- 20221114
LR  - 20221201
IS  - 1367-4811 (Electronic)
IS  - 1367-4803 (Linking)
VI  - 38
IP  - 9
DP  - 2022 Apr 28
TI  - HAMdetector: a Bayesian regression model that integrates information to detect 
      HLA-associated mutations.
PG  - 2428-2436
LID - 10.1093/bioinformatics/btac134 [doi]
AB  - MOTIVATION: A key process in anti-viral adaptive immunity is that the human 
      leukocyte antigen (HLA) system presents epitopes as major histocompatibility 
      complex I (MHC I) protein-peptide complexes on cell surfaces and in this way 
      alerts CD8+ cytotoxic T-lymphocytes (CTLs). This pathway exerts strong selection 
      pressure on viruses, favoring viral mutants that escape recognition by the 
      HLA/CTL system. Naturally, such immune escape mutations often emerge in highly 
      variable viruses, e.g. HIV or HBV, as HLA-associated mutations (HAMs), specific 
      to the hosts MHC I proteins. The reliable identification of HAMs is not only 
      important for understanding viral genomes and their evolution, but it also 
      impacts the development of broadly effective anti-viral treatments and vaccines 
      against variable viruses. By their very nature, HAMs are amenable to detection by 
      statistical methods in paired sequence/HLA data. However, HLA alleles are very 
      polymorphic in the human host population which makes the available data 
      relatively sparse and noisy. Under these circumstances, one way to optimize HAM 
      detection is to integrate all relevant information in a coherent model. Bayesian 
      inference offers a principled approach to achieve this. RESULTS: We present a new 
      Bayesian regression model for the detection of HAMs that integrates a 
      sparsity-inducing prior, epitope predictions and phylogenetic bias assessment, 
      and that yields easily interpretable quantitative information on HAM candidates. 
      The model predicts experimentally confirmed HAMs as having high posterior 
      probabilities, and it performs well in comparison to state-of-the-art models for 
      several datasets from individuals infected with HBV, HDV and HIV. AVAILABILITY 
      AND IMPLEMENTATION: The source code of this software is available at 
      https://github.com/HAMdetector/Escape.jl under a permissive MIT license. The data 
      underlying this article were provided by permission. Data will be shared on 
      request to the corresponding author with permission of the respective co-authors. 
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics 
      online.
CI  - (c) The Author(s) 2022. Published by Oxford University Press. All rights reserved. 
      For permissions, please e-mail: journals.permissions@oup.com.
FAU - Habermann, Daniel
AU  - Habermann D
AUID- ORCID: 0000-0003-3685-7287
AD  - Bioinformatics and Computational Biophysics, Faculty of Biology, University of 
      Duisburg-Essen, Essen 45117, Germany.
FAU - Kharimzadeh, Hadi
AU  - Kharimzadeh H
AD  - Division of Clinical Pharmacology, University Hospital, LMU Munich, Munich, 
      Germany.
FAU - Walker, Andreas
AU  - Walker A
AD  - Institute of Virology, Medical Faculty, University Hospital Dusseldorf, 
      Heinrich-Heine-Universitat, Dusseldorf 40225, Germany.
FAU - Li, Yang
AU  - Li Y
AD  - AIDS and HIV Research Group, State Key Laboratory of Virology, Wuhan Institute of 
      Virology, Chinese Academy of Science, Wuhan, China.
FAU - Yang, Rongge
AU  - Yang R
AD  - AIDS and HIV Research Group, State Key Laboratory of Virology, Wuhan Institute of 
      Virology, Chinese Academy of Science, Wuhan, China.
FAU - Kaiser, Rolf
AU  - Kaiser R
AD  - Institute of Virology, University of Cologne, Faculty of Medicine and University 
      Hospital of Cologne, Cologne 50935, Germany.
FAU - Brumme, Zabrina L
AU  - Brumme ZL
AD  - Faculty of Health Sciences, Simon Fraser University, Burnaby, Canada.
AD  - British Columbia Centre for Excellence in HIV/AIDS, Vancouver, Canada.
FAU - Timm, Jorg
AU  - Timm J
AD  - Institute of Virology, Medical Faculty, University Hospital Dusseldorf, 
      Heinrich-Heine-Universitat, Dusseldorf 40225, Germany.
FAU - Roggendorf, Michael
AU  - Roggendorf M
AD  - Institute of Virology, School of Medicine, Technical University of 
      Munich/Helmholtz Zentrum Munchen, Munich, Germany.
FAU - Hoffmann, Daniel
AU  - Hoffmann D
AUID- ORCID: 0000-0003-2973-7869
AD  - Bioinformatics and Computational Biophysics, Faculty of Biology, University of 
      Duisburg-Essen, Essen 45117, Germany.
AD  - Center of Medical Biotechnology, University of Duisburg-Essen, Essen, Germany.
AD  - Center for Computational Sciences and Simulation, University of Duisburg-Essen, 
      Essen, Germany.
LA  - eng
GR  - PJT-148621/Canadian Institutes for Health Research/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Bioinformatics
JT  - Bioinformatics (Oxford, England)
JID - 9808944
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (HLA Antigens)
RN  - 0 (Epitopes)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Epitopes, T-Lymphocyte)
SB  - IM
MH  - Humans
MH  - Phylogeny
MH  - Bayes Theorem
MH  - *Histocompatibility Antigens Class I
MH  - HLA Antigens/genetics
MH  - Mutation
MH  - Epitopes
MH  - Histocompatibility Antigens Class II
MH  - *HIV Infections
MH  - Epitopes, T-Lymphocyte/genetics
EDAT- 2022/03/04 06:00
MHDA- 2022/11/15 06:00
CRDT- 2022/03/03 08:55
PHST- 2021/07/22 00:00 [received]
PHST- 2021/11/21 00:00 [revised]
PHST- 2022/02/28 00:00 [accepted]
PHST- 2022/03/04 06:00 [pubmed]
PHST- 2022/11/15 06:00 [medline]
PHST- 2022/03/03 08:55 [entrez]
AID - 6541628 [pii]
AID - 10.1093/bioinformatics/btac134 [doi]
PST - ppublish
SO  - Bioinformatics. 2022 Apr 28;38(9):2428-2436. doi: 10.1093/bioinformatics/btac134.