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SampPick: Selection of a Cohort of Subjects Matching a Population HLA Distribution

Immune responses to therapeutic proteins and peptides can adversely affect their safety and efficacy; consequently, immunogenicity risk-assessments are part of the development, licensure and clinical use of these products. In most cases the development of anti-drug antibodies is mediated by T cells...

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Autores principales: McGill, Joseph R., Yogurtcu, Osman N., Verthelyi, Daniela, Yang, Hong, Sauna, Zuben E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6933600/
https://www.ncbi.nlm.nih.gov/pubmed/31921155
http://dx.doi.org/10.3389/fimmu.2019.02894
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author McGill, Joseph R.
Yogurtcu, Osman N.
Verthelyi, Daniela
Yang, Hong
Sauna, Zuben E.
author_facet McGill, Joseph R.
Yogurtcu, Osman N.
Verthelyi, Daniela
Yang, Hong
Sauna, Zuben E.
author_sort McGill, Joseph R.
collection PubMed
description Immune responses to therapeutic proteins and peptides can adversely affect their safety and efficacy; consequently, immunogenicity risk-assessments are part of the development, licensure and clinical use of these products. In most cases the development of anti-drug antibodies is mediated by T cells which requires antigen presentation by Major Histocompatibility Complex Class II (MHCII) molecules (also called Human Leucocyte Antigen, HLA in humans). Immune responses to many protein therapeutics are thus HLA-restricted and it is important that the distribution of HLA variants used in the immunogenicity assessments provides adequate coverage of the target population. Due to biases inherent to the collection of samples in a blood bank or donor pool, simple random sampling will not achieve a truly representative sample of the population of interest. To help select a donor cohort we introduce SampPick, an implementation of simulated annealing which optimizes cohort selection to closely match the frequency distribution of a target population or subpopulation. With inputs of a target background frequency distribution for a population and a set of available, HLA-typed donors, the algorithm will iteratively create a cohort of donors of a user selected size that will closely match the target population rather than a random sample. In addition to optimizing the HLA types of donor cohorts, the software presented can be used to optimize donor cohorts for any other biallelic or monoallelic trait.
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spelling pubmed-69336002020-01-09 SampPick: Selection of a Cohort of Subjects Matching a Population HLA Distribution McGill, Joseph R. Yogurtcu, Osman N. Verthelyi, Daniela Yang, Hong Sauna, Zuben E. Front Immunol Immunology Immune responses to therapeutic proteins and peptides can adversely affect their safety and efficacy; consequently, immunogenicity risk-assessments are part of the development, licensure and clinical use of these products. In most cases the development of anti-drug antibodies is mediated by T cells which requires antigen presentation by Major Histocompatibility Complex Class II (MHCII) molecules (also called Human Leucocyte Antigen, HLA in humans). Immune responses to many protein therapeutics are thus HLA-restricted and it is important that the distribution of HLA variants used in the immunogenicity assessments provides adequate coverage of the target population. Due to biases inherent to the collection of samples in a blood bank or donor pool, simple random sampling will not achieve a truly representative sample of the population of interest. To help select a donor cohort we introduce SampPick, an implementation of simulated annealing which optimizes cohort selection to closely match the frequency distribution of a target population or subpopulation. With inputs of a target background frequency distribution for a population and a set of available, HLA-typed donors, the algorithm will iteratively create a cohort of donors of a user selected size that will closely match the target population rather than a random sample. In addition to optimizing the HLA types of donor cohorts, the software presented can be used to optimize donor cohorts for any other biallelic or monoallelic trait. Frontiers Media S.A. 2019-12-20 /pmc/articles/PMC6933600/ /pubmed/31921155 http://dx.doi.org/10.3389/fimmu.2019.02894 Text en Copyright © 2019 McGill, Yogurtcu, Verthelyi, Yang and Sauna. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
McGill, Joseph R.
Yogurtcu, Osman N.
Verthelyi, Daniela
Yang, Hong
Sauna, Zuben E.
SampPick: Selection of a Cohort of Subjects Matching a Population HLA Distribution
title SampPick: Selection of a Cohort of Subjects Matching a Population HLA Distribution
title_full SampPick: Selection of a Cohort of Subjects Matching a Population HLA Distribution
title_fullStr SampPick: Selection of a Cohort of Subjects Matching a Population HLA Distribution
title_full_unstemmed SampPick: Selection of a Cohort of Subjects Matching a Population HLA Distribution
title_short SampPick: Selection of a Cohort of Subjects Matching a Population HLA Distribution
title_sort samppick: selection of a cohort of subjects matching a population hla distribution
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6933600/
https://www.ncbi.nlm.nih.gov/pubmed/31921155
http://dx.doi.org/10.3389/fimmu.2019.02894
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