Network-based methods for identifying critical pathways of complex diseases: a survey

Zhang, Qiaosheng; Li, Jie; Xue, Hanqing; Kong, Leilei; Wang, Yadong

doi:10.1039/c5mb00815h

Cited by 18 publications

(13 citation statements)

References 45 publications

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“…Network-based analyses aim to systematically integrate measurements from high-throughput data to gain a global understanding of cellular function under changing conditions, e.g. different disease sub-types, progressive stages of cancer and drug [9,10].…”

Section: Introductionmentioning

confidence: 99%

ACE2 Protein-protein Interaction Networks Reveal Potential Druggable Targets for SARS-CoV-2

Xia¹,

Chen²,

Zhou³

et al. 2020

Preprint

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Background The novel coronavirus SARS-CoV-2 pandemic has infected more than 10 million people, killed over 500,000 so far. Currently, no effective drugs are available to treat this infectious disease, due to limited knowledge of the molecular mechanisms of SARS-CoV-2 infection. ACE2 (angiotensin I converting enzyme 2) has long been identified as the major receptor for coronavirus entry the host cells. Methods In this study, we constructed the protein-protein interaction networks (PPIN) based on ACE2 and its interacting proteins, combined with the expression change and co-expression relationship. The potential drugs targeting the proteins in the PPIN were explored.Results ACE2 and its interacting proteins AAMP and HRAS are obviously increased, and their PPIN show distinguishing expression patterns during the COVID-19 progression. At least six pathways are activated for the host cell in the response to the virus. Moreover, drug-target networks were built to provide important clues to block ACE2 and its interacting proteins. Except the reported four drugs for ACE2, its interacting protein CALM1 and HRAS are great potentially druggable. We also considered the path initiated from ACE2 to nucleus by cascades of interaction, especially for the transcription factors in the PPIN which are also druggable. Conclusion In summary, this study provides new insight into the disruption of the biological response to virus mediated by ACE2, but also its cascade interacting proteins when considering of PPIN.

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Section: Introductionmentioning

confidence: 99%

ACE2 Protein-protein Interaction Networks Reveal Potential Druggable Targets for SARS-CoV-2

Xia¹,

Chen²,

Zhou³

et al. 2020

Preprint

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“…Therefore, pathway-based analysis of complex diseases has become a research hotspot. To date, these methods have entered the third stage [45]: 1) Pathway-based gene set enrichment analysis; 2) Pathway-based functional class clustering and scoring approaches; and 3) Network-based pathway approaches.…”

Section: Resultsmentioning

confidence: 99%

A network-based pathway-expanding approach for pathway analysis

Zhang

Xie

et al. 2016

BMC Bioinformatics

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BackgroundPathway analysis combining multiple types of high-throughput data, such as genomics and proteomics, has become the first choice to gain insights into the pathogenesis of complex diseases. Currently, several pathway analysis methods have been developed to study complex diseases. However, these methods did not take into account the interaction between internal and external genes of the pathway and between pathways. Hence, these approaches still face some challenges. Here, we propose a network-based pathway-expanding approach that takes the topological structures of biological networks into account.ResultsFirst, two weighted gene-gene interaction networks (tumor and normal) are constructed integrating protein-protein interaction(PPI) information, gene expression data and pathway databases. Then, they are used to identify significant pathways through testing the difference of topological structures of expanded pathways in the two weighted networks. The proposed method is employed to analyze two breast cancer data. As a result, the top 15 pathways identified using the proposed method are supported by biological knowledge from the published literatures and other methods. In addition, the proposed method is also compared with other methods, such as GSEA and SPIA, and estimated using the classification performance of the top 15 expanded pathways.ConclusionsA novel network-based pathway-expanding approach is proposed to avoid the limitations of existing pathway analysis approaches. Experimental results indicate that the proposed method can accurately and reliably identify significant pathways which are related to the corresponding disease.Electronic supplementary materialThe online version of this article (doi:10.1186/s12859-016-1333-x) contains supplementary material, which is available to authorized users.

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“…Analyses based on protein-protein interaction networks (PPINs) have become a prevalent method for the high-throughput data, especially the protein interaction data [8]. PPINs analysis can systematically integrate single or multiple high-throughput data to obtain a global understanding of cellular functions or processes under various conditions, e.g., different tumor sub-types, cancer progressive stages and cell sub-groups [9,10].…”

Section: Introductionmentioning

confidence: 99%

ACE2 Protein-Protein Interaction Networks Reveal Potential Druggable Targets For SARS-CoV-2

Xia

Zhou

Chen

et al. 2021

Preprint

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Background: The novel coronavirus SARS-CoV-2 pandemic has infected more than 130 million people, killed over 2.3 million so far. Currently, no effective drugs are available to treat this infectious disease, due to limited knowledge of the molecular mechanisms of SARS-CoV-2 infection. ACE2 (angiotensin I converting enzyme 2) has long been identified as the major receptor for coronavirus entry the host cells. Methods: In this study, we constructed the protein-protein interaction networks (PPIN) based on ACE2 and its interacting proteins, considering with the expression alternation and co-expression relationship. The potential drugs targeting the proteins in the PPIN were explored.Results: ACE2 and its interacting proteins AAMP and HRAS are obviously increased, and their PPIN show distinguishing expression patterns during the COVID-19 progression. At least six pathways are activated for the host cell in the response to the virus. Moreover, drug-target networks were built to provide important clues to block ACE2 and its interacting proteins. Except the reported four drugs for ACE2, its interacting protein CALM1 and HRAS are great potentially druggable. We also considered the path initiated from ACE2 to nucleus by cascades of interaction, especially for the transcription factors in the PPIN which are also druggable.Conclusion: In summary, this study provides new insight into the disruption of the biological response to virus mediated by ACE2, but also its cascade interacting proteins when considering of PPIN.

show abstract

Network-based methods for identifying critical pathways of complex diseases: a survey

Cited by 18 publications

References 45 publications

ACE2 Protein-protein Interaction Networks Reveal Potential Druggable Targets for SARS-CoV-2

ACE2 Protein-protein Interaction Networks Reveal Potential Druggable Targets for SARS-CoV-2

A network-based pathway-expanding approach for pathway analysis

ACE2 Protein-Protein Interaction Networks Reveal Potential Druggable Targets For SARS-CoV-2

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