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From the reference human genome to human pangenome: Premise, promise and challenge

The Reference Human Genome remains the single most important resource for mapping genetic variations and assessing their impact. However, it is monophasic, incomplete and not representative of the variation that exists in the population. Given the extent of ethno-geographic diversity and the consequ...

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Autores principales: Singh, Vipin, Pandey, Shweta, Bhardwaj, Anshu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9684177/
https://www.ncbi.nlm.nih.gov/pubmed/36437921
http://dx.doi.org/10.3389/fgene.2022.1042550
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author Singh, Vipin
Pandey, Shweta
Bhardwaj, Anshu
author_facet Singh, Vipin
Pandey, Shweta
Bhardwaj, Anshu
author_sort Singh, Vipin
collection PubMed
description The Reference Human Genome remains the single most important resource for mapping genetic variations and assessing their impact. However, it is monophasic, incomplete and not representative of the variation that exists in the population. Given the extent of ethno-geographic diversity and the consequent diversity in clinical manifestations of these variations, population specific references were developed overtime. The dramatically plummeting cost of sequencing whole genomes and the advent of third generation long range sequencers allowing accurate, error free, telomere-to-telomere assemblies of human genomes present us with a unique and unprecedented opportunity to develop a more composite standard reference consisting of a collection of multiple genomes that capture the maximal variation existing in the population, with the deepest annotation possible, enabling a realistic, reliable and actionable estimation of clinical significance of specific variations. The Human Pangenome Project thus is a logical next step promising a more accurate and global representation of genomic variations. The pangenome effort must be reciprocally complemented with precise variant discovery tools and exhaustive annotation to ensure unambiguous clinical assessment of the variant in ethno-geographical context. Here we discuss a broad roadmap, the challenges and way forward in developing a universal pangenome reference including data visualization techniques and integration of prior knowledge base in the new graph based architecture and tools to submit, compare, query, annotate and retrieve relevant information from the pangenomes. The biggest challenge, however, will be the ethical, legal and social implications and the training of human resource to the new reference paradigm.
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spelling pubmed-96841772022-11-25 From the reference human genome to human pangenome: Premise, promise and challenge Singh, Vipin Pandey, Shweta Bhardwaj, Anshu Front Genet Genetics The Reference Human Genome remains the single most important resource for mapping genetic variations and assessing their impact. However, it is monophasic, incomplete and not representative of the variation that exists in the population. Given the extent of ethno-geographic diversity and the consequent diversity in clinical manifestations of these variations, population specific references were developed overtime. The dramatically plummeting cost of sequencing whole genomes and the advent of third generation long range sequencers allowing accurate, error free, telomere-to-telomere assemblies of human genomes present us with a unique and unprecedented opportunity to develop a more composite standard reference consisting of a collection of multiple genomes that capture the maximal variation existing in the population, with the deepest annotation possible, enabling a realistic, reliable and actionable estimation of clinical significance of specific variations. The Human Pangenome Project thus is a logical next step promising a more accurate and global representation of genomic variations. The pangenome effort must be reciprocally complemented with precise variant discovery tools and exhaustive annotation to ensure unambiguous clinical assessment of the variant in ethno-geographical context. Here we discuss a broad roadmap, the challenges and way forward in developing a universal pangenome reference including data visualization techniques and integration of prior knowledge base in the new graph based architecture and tools to submit, compare, query, annotate and retrieve relevant information from the pangenomes. The biggest challenge, however, will be the ethical, legal and social implications and the training of human resource to the new reference paradigm. Frontiers Media S.A. 2022-11-10 /pmc/articles/PMC9684177/ /pubmed/36437921 http://dx.doi.org/10.3389/fgene.2022.1042550 Text en Copyright © 2022 Singh, Pandey and Bhardwaj. https://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 Genetics
Singh, Vipin
Pandey, Shweta
Bhardwaj, Anshu
From the reference human genome to human pangenome: Premise, promise and challenge
title From the reference human genome to human pangenome: Premise, promise and challenge
title_full From the reference human genome to human pangenome: Premise, promise and challenge
title_fullStr From the reference human genome to human pangenome: Premise, promise and challenge
title_full_unstemmed From the reference human genome to human pangenome: Premise, promise and challenge
title_short From the reference human genome to human pangenome: Premise, promise and challenge
title_sort from the reference human genome to human pangenome: premise, promise and challenge
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9684177/
https://www.ncbi.nlm.nih.gov/pubmed/36437921
http://dx.doi.org/10.3389/fgene.2022.1042550
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