Dataset Information

Construction and analysis of sample-specific driver modules for breast cancer.

ABSTRACT:

Background

It is important to understand the functional impact of somatic mutation and methylation aberration at an individual level to implement precision medicine. Recent studies have demonstrated that the perturbation of gene interaction networks can provide a fundamental link between genotype (or epigenotype) and phenotype. However, it is unclear how individual mutations affect the function of biological networks, especially for individual methylation aberration. To solve this, we provided a sample-specific driver module construction method using the 2-order network theory and hub-gene theory to identify individual perturbation networks driven by mutations or methylation aberrations.

Results

Our method integrated multi-omics of breast cancer, including genomics, transcriptomics, epigenomics and interactomics, and provided new insight into the synergistic collaboration between methylation and mutation at an individual level. A common driver pattern of breast cancer was identified from a novel perspective of a driver module, which is correlated to the occurrence and development of breast cancer. The constructed driver module reflects the survival prognosis and degree of malignancy among different subtypes of breast cancer. Additionally, subtype-specific driver modules were identified.

Conclusions

This study explores the driver module of individual cancer, and contributes to a better understanding of the mechanism of breast cancer driven by the mutations and methylation variations from the point of view of the driver network. This work will help identify new therapeutic combinations of gene mutations and drugs in humans.

SUBMITTER: Chen Y

PROVIDER: S-EPMC9583575 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Publications

Construction and analysis of sample-specific driver modules for breast cancer.

Chen Yuanyuan Y Li Haitao H Sun Xiao X

BMC genomics 20221020 1

<h4>Background</h4>It is important to understand the functional impact of somatic mutation and methylation aberration at an individual level to implement precision medicine. Recent studies have demonstrated that the perturbation of gene interaction networks can provide a fundamental link between genotype (or epigenotype) and phenotype. However, it is unclear how individual mutations affect the function of biological networks, especially for individual methylation aberration. To solve this, we pr ...[more]

PMID: 36266635

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Project description:MotivationProtein phosphorylation is a ubiquitous mechanism of post-translational modification that plays a central role in cellular signaling. Phosphorylation is particularly important in the context of cancer, as downregulation of tumor suppressors and upregulation of oncogenes by the dysregulation of associated kinase and phosphatase networks are shown to have key roles in tumor growth and progression. Despite recent advances that enable large-scale monitoring of protein phosphorylation, these data are not fully incorporated into such computational tasks as phenotyping and subtyping of cancers.ResultsWe develop a network-based algorithm, CoPPNet, to enable unsupervised subtyping of cancers using phosphorylation data. For this purpose, we integrate prior knowledge on evolutionary, structural and functional association of phosphosites, kinase-substrate associations and protein-protein interactions with the correlation of phosphorylation of phosphosites across different tumor samples (a.k.a co-phosphorylation) to construct a context-specific-weighted network of phosphosites. We then mine these networks to identify subnetworks with correlated phosphorylation patterns. We apply the proposed framework to two mass-spectrometry-based phosphorylation datasets for breast cancer (BC), and observe that (i) the phosphorylation pattern of the identified subnetworks are highly correlated with clinically identified subtypes, and (ii) the identified subnetworks are highly reproducible across datasets that are derived from different studies. Our results show that integration of quantitative phosphorylation data with network frameworks can provide mechanistic insights into the differences between the signaling mechanisms that drive BC subtypes. Furthermore, the reproducibility of the identified subnetworks suggests that phosphorylation can provide robust classification of disease response and markers.Availability and implementationCoPPNet is available at http://compbio.case.edu/coppnet/.Supplementary informationSupplementary data are available at Bioinformatics online.

Dataset Information

Construction and analysis of sample-specific driver modules for breast cancer.

Background

Results

Conclusions

Publications

Construction and analysis of sample-specific driver modules for breast cancer.

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