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Systems biology as a comparative approach to understand complex gene expression in neurological diseases.

ABSTRACT: Systems biology interdisciplinary approaches have become an essential analytical tool that may yield novel and powerful insights about the nature of human health and disease. Complex disorders are known to be caused by the combination of genetic, environmental, immunological or neurological factors. Thus, to understand such disorders, it becomes necessary to address the study of this complexity from a novel perspective. Here, we present a review of integrative approaches that help to understand the underlying biological processes involved in the etiopathogenesis of neurological diseases, for example, those related to autism and autism spectrum disorders (ASD) endophenotypes. Furthermore, we highlight the role of systems biology in the discovery of new biomarkers or therapeutic targets in complex disorders, a key step in the development of personalized medicine, and we demonstrate the role of systems approaches in the design of classifiers that can shorten the time for behavioral diagnosis of autism.

SUBMITTER: Diaz-Beltran L

PROVIDER: S-EPMC4217627 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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Systems biology as a comparative approach to understand complex gene expression in neurological diseases.

Diaz-Beltran Leticia L Cano Carlos C Wall Dennis P DP Esteban Francisco J FJ

Behavioral sciences (Basel, Switzerland) 20130521 2

Systems biology interdisciplinary approaches have become an essential analytical tool that may yield novel and powerful insights about the nature of human health and disease. Complex disorders are known to be caused by the combination of genetic, environmental, immunological or neurological factors. Thus, to understand such disorders, it becomes necessary to address the study of this complexity from a novel perspective. Here, we present a review of integrative approaches that help to understand ...[more]

PMID: 25379238

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Project description:Racial disparities between Black/African Americans (AA) and White patients in colorectal cancer are an ever-growing area of concern. Black/AA show the highest incidence and have the highest mortality among major U.S. racial groups. There is no definite cause other than possible sociodemographic, socioeconomic, education, nutrition, delivery of healthcare, screening, and cultural factors. A primary limitation in this field is the lack of and small sample size of Black/AA studies. Thus, this study aimed to investigate whether differences in gene expression contribute to this ongoing unanswered racial disparity issue. In this study, we examined transcriptomic data of Black/AA and White patient cohorts using a bioinformatic and systems biology approach. We performed a Kaplan-Meier overall survival analysis between both patient cohorts across critical colorectal cancer signal transduction networks (STN), to determine the differences in significant genes across each cohort. Other bioinformatic analyses performed included PROGENy (pathway responsive genes for activity inference), RNA sequencing differential expression using DESeq2, multivariable-adjusted regression, and other associated Kaplan-Meier analyses. These analyses identified novel prognostic genes independent from each cohort, 176 differentially expressed genes, and specific patient cohort STN survival associations. Despite the overarching limitation, the results revealed several novel differences in gene expression between the colorectal cancer Black/AA and White patient cohorts, which allows one to dive deeper into and understand the behavior on a systems level of what could be driving this racial difference across colorectal cancer. Concretely, this information can guide precision medicine approaches tailored specifically for colorectal cancer racial disparities.SignificanceThe purpose of this work is to investigate the racial disparities in colorectal cancer between Black/AA and White patient cohorts using a systems biology and bioinformatic approach. Our study investigates the underlying biology of each patient cohort. Concretely, the findings of this study include disparity-associated genes and pathways, which provide a tangible starting point to guide precision medicine approaches tailored specifically for colorectal cancer racial disparities.

Dataset Information

Systems biology as a comparative approach to understand complex gene expression in neurological diseases.

Publications

Systems biology as a comparative approach to understand complex gene expression in neurological diseases.

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