DeltaNeTS+: elucidating the mechanism of drugs and diseases using gene expression and transcriptional regulatory networks
Abstract Background Knowledge on the molecular targets of diseases and drugs is crucial for elucidating disease pathogenesis and mechanism of action of drugs, and for driving drug discovery and treatment formulation. In this regard, high-throughput gene transcriptional profiling has become a leading...
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crspringernat:10.1186/s12859-021-04046-2 2023-05-15T15:34:35+02:00 DeltaNeTS+: elucidating the mechanism of drugs and diseases using gene expression and transcriptional regulatory networks Noh, Heeju Hua, Ziyi Chrysinas, Panagiotis Shoemaker, Jason E. Gunawan, Rudiyanto Eidgenössische Technische Hochschule Zürich 2021 http://dx.doi.org/10.1186/s12859-021-04046-2 http://link.springer.com/content/pdf/10.1186/s12859-021-04046-2.pdf http://link.springer.com/article/10.1186/s12859-021-04046-2/fulltext.html en eng Springer Science and Business Media LLC http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/ CC-BY BMC Bioinformatics volume 22, issue 1 ISSN 1471-2105 Applied Mathematics Computer Science Applications Molecular Biology Biochemistry Structural Biology journal-article 2021 crspringernat https://doi.org/10.1186/s12859-021-04046-2 2022-01-04T07:20:31Z Abstract Background Knowledge on the molecular targets of diseases and drugs is crucial for elucidating disease pathogenesis and mechanism of action of drugs, and for driving drug discovery and treatment formulation. In this regard, high-throughput gene transcriptional profiling has become a leading technology, generating whole-genome data on the transcriptional alterations caused by diseases or drug compounds. However, identifying direct gene targets, especially in the background of indirect (downstream) effects, based on differential gene expressions is difficult due to the complexity of gene regulatory network governing the gene transcriptional processes. Results In this work, we developed a network analysis method, called DeltaNeTS+, for inferring direct gene targets of drugs and diseases from gene transcriptional profiles. DeltaNeTS+ uses a gene regulatory network model to identify direct perturbations to the transcription of genes using gene expression data. Importantly, DeltaNeTS+ is able to combine both steady-state and time-course expression profiles, as well as leverage information on the gene network structure. We demonstrated the power of DeltaNeTS+ in predicting gene targets using gene expression data in complex organisms, including Caenorhabditis elegans and human cell lines (T-cell and Calu-3). More specifically, in an application to time-course gene expression profiles of influenza A H1N1 (swine flu) and H5N1 (avian flu) infection, DeltaNeTS+ shed light on the key differences of dynamic cellular perturbations caused by the two influenza strains. Conclusion DeltaNeTS+ is a powerful network analysis tool for inferring gene targets from gene expression profiles. As demonstrated in the case studies, by incorporating available information on gene network structure, DeltaNeTS+ produces accurate predictions of direct gene targets from a small sample size (~ 10 s). Integrating static and dynamic expression data with transcriptional network structure extracted from genomic information, as enabled by DeltaNeTS+, is crucial toward personalized medicine, where treatments can be tailored to individual patients. DeltaNeTS+ can be freely downloaded from http://www.github.com/cabsel/deltanetsplus . Article in Journal/Newspaper Avian flu Springer Nature (via Crossref) BMC Bioinformatics 22 1 |
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English |
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Applied Mathematics Computer Science Applications Molecular Biology Biochemistry Structural Biology |
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Applied Mathematics Computer Science Applications Molecular Biology Biochemistry Structural Biology Noh, Heeju Hua, Ziyi Chrysinas, Panagiotis Shoemaker, Jason E. Gunawan, Rudiyanto DeltaNeTS+: elucidating the mechanism of drugs and diseases using gene expression and transcriptional regulatory networks |
topic_facet |
Applied Mathematics Computer Science Applications Molecular Biology Biochemistry Structural Biology |
description |
Abstract Background Knowledge on the molecular targets of diseases and drugs is crucial for elucidating disease pathogenesis and mechanism of action of drugs, and for driving drug discovery and treatment formulation. In this regard, high-throughput gene transcriptional profiling has become a leading technology, generating whole-genome data on the transcriptional alterations caused by diseases or drug compounds. However, identifying direct gene targets, especially in the background of indirect (downstream) effects, based on differential gene expressions is difficult due to the complexity of gene regulatory network governing the gene transcriptional processes. Results In this work, we developed a network analysis method, called DeltaNeTS+, for inferring direct gene targets of drugs and diseases from gene transcriptional profiles. DeltaNeTS+ uses a gene regulatory network model to identify direct perturbations to the transcription of genes using gene expression data. Importantly, DeltaNeTS+ is able to combine both steady-state and time-course expression profiles, as well as leverage information on the gene network structure. We demonstrated the power of DeltaNeTS+ in predicting gene targets using gene expression data in complex organisms, including Caenorhabditis elegans and human cell lines (T-cell and Calu-3). More specifically, in an application to time-course gene expression profiles of influenza A H1N1 (swine flu) and H5N1 (avian flu) infection, DeltaNeTS+ shed light on the key differences of dynamic cellular perturbations caused by the two influenza strains. Conclusion DeltaNeTS+ is a powerful network analysis tool for inferring gene targets from gene expression profiles. As demonstrated in the case studies, by incorporating available information on gene network structure, DeltaNeTS+ produces accurate predictions of direct gene targets from a small sample size (~ 10 s). Integrating static and dynamic expression data with transcriptional network structure extracted from genomic information, as enabled by DeltaNeTS+, is crucial toward personalized medicine, where treatments can be tailored to individual patients. DeltaNeTS+ can be freely downloaded from http://www.github.com/cabsel/deltanetsplus . |
author2 |
Eidgenössische Technische Hochschule Zürich |
format |
Article in Journal/Newspaper |
author |
Noh, Heeju Hua, Ziyi Chrysinas, Panagiotis Shoemaker, Jason E. Gunawan, Rudiyanto |
author_facet |
Noh, Heeju Hua, Ziyi Chrysinas, Panagiotis Shoemaker, Jason E. Gunawan, Rudiyanto |
author_sort |
Noh, Heeju |
title |
DeltaNeTS+: elucidating the mechanism of drugs and diseases using gene expression and transcriptional regulatory networks |
title_short |
DeltaNeTS+: elucidating the mechanism of drugs and diseases using gene expression and transcriptional regulatory networks |
title_full |
DeltaNeTS+: elucidating the mechanism of drugs and diseases using gene expression and transcriptional regulatory networks |
title_fullStr |
DeltaNeTS+: elucidating the mechanism of drugs and diseases using gene expression and transcriptional regulatory networks |
title_full_unstemmed |
DeltaNeTS+: elucidating the mechanism of drugs and diseases using gene expression and transcriptional regulatory networks |
title_sort |
deltanets+: elucidating the mechanism of drugs and diseases using gene expression and transcriptional regulatory networks |
publisher |
Springer Science and Business Media LLC |
publishDate |
2021 |
url |
http://dx.doi.org/10.1186/s12859-021-04046-2 http://link.springer.com/content/pdf/10.1186/s12859-021-04046-2.pdf http://link.springer.com/article/10.1186/s12859-021-04046-2/fulltext.html |
genre |
Avian flu |
genre_facet |
Avian flu |
op_source |
BMC Bioinformatics volume 22, issue 1 ISSN 1471-2105 |
op_rights |
http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/ |
op_rightsnorm |
CC-BY |
op_doi |
https://doi.org/10.1186/s12859-021-04046-2 |
container_title |
BMC Bioinformatics |
container_volume |
22 |
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1 |
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