Cargando…

Applying Expression Profile Similarity for Discovery of Patient-Specific Functional Mutations

The progress of cancer genome sequencing projects yields unprecedented information of mutations for numerous patients. However, the complexity of mutation profiles of cancer patients hinders the further understanding to mechanisms of oncogenesis. One basic question is how to find mutations with func...

Descripción completa

Detalles Bibliográficos
Autor principal: Meng, Guofeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5876532/
https://www.ncbi.nlm.nih.gov/pubmed/29485617
http://dx.doi.org/10.3390/ht7010006
_version_ 1783310529402503168
author Meng, Guofeng
author_facet Meng, Guofeng
author_sort Meng, Guofeng
collection PubMed
description The progress of cancer genome sequencing projects yields unprecedented information of mutations for numerous patients. However, the complexity of mutation profiles of cancer patients hinders the further understanding to mechanisms of oncogenesis. One basic question is how to find mutations with functional impacts. In this work, we introduce a computational method to predict functional somatic mutations of each patient by integrating mutation recurrence with expression profile similarity. With this method, the functional mutations are determined by checking the mutation enrichment among a group of patients with similar expression profiles. We applied this method to three cancer types and identified the functional mutations. Comparison of the predictions for three cancer types suggested that most of the functional mutations were cancer-type-specific with one exception to p53. By checking predicted results, we found that our method effectively filtered non-functional mutations resulting from large protein sizes. In addition, this method can also perform functional annotation to each patient to describe their association with signalling pathways or biological processes. In breast cancer, we predicted “cell adhesion” and other terms to be significantly associated with oncogenesis.
format Online
Article
Text
id pubmed-5876532
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-58765322018-04-09 Applying Expression Profile Similarity for Discovery of Patient-Specific Functional Mutations Meng, Guofeng High Throughput Article The progress of cancer genome sequencing projects yields unprecedented information of mutations for numerous patients. However, the complexity of mutation profiles of cancer patients hinders the further understanding to mechanisms of oncogenesis. One basic question is how to find mutations with functional impacts. In this work, we introduce a computational method to predict functional somatic mutations of each patient by integrating mutation recurrence with expression profile similarity. With this method, the functional mutations are determined by checking the mutation enrichment among a group of patients with similar expression profiles. We applied this method to three cancer types and identified the functional mutations. Comparison of the predictions for three cancer types suggested that most of the functional mutations were cancer-type-specific with one exception to p53. By checking predicted results, we found that our method effectively filtered non-functional mutations resulting from large protein sizes. In addition, this method can also perform functional annotation to each patient to describe their association with signalling pathways or biological processes. In breast cancer, we predicted “cell adhesion” and other terms to be significantly associated with oncogenesis. MDPI 2018-02-22 /pmc/articles/PMC5876532/ /pubmed/29485617 http://dx.doi.org/10.3390/ht7010006 Text en © 2018 by the author. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Meng, Guofeng
Applying Expression Profile Similarity for Discovery of Patient-Specific Functional Mutations
title Applying Expression Profile Similarity for Discovery of Patient-Specific Functional Mutations
title_full Applying Expression Profile Similarity for Discovery of Patient-Specific Functional Mutations
title_fullStr Applying Expression Profile Similarity for Discovery of Patient-Specific Functional Mutations
title_full_unstemmed Applying Expression Profile Similarity for Discovery of Patient-Specific Functional Mutations
title_short Applying Expression Profile Similarity for Discovery of Patient-Specific Functional Mutations
title_sort applying expression profile similarity for discovery of patient-specific functional mutations
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5876532/
https://www.ncbi.nlm.nih.gov/pubmed/29485617
http://dx.doi.org/10.3390/ht7010006
work_keys_str_mv AT mengguofeng applyingexpressionprofilesimilarityfordiscoveryofpatientspecificfunctionalmutations