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Personalized analysis of breast cancer using sample-specific networks.

ABSTRACT: Breast cancer is a disease with high heterogeneity. Cancer is not usually caused by a single gene, but by multiple genes and their interactions with others and surroundings. Estimating breast cancer-specific gene-gene interaction networks is critical to elucidate the mechanisms of breast cancer from a biological network perspective. In this study, sample-specific gene-gene interaction networks of breast cancer samples were established by using a sample-specific network analysis method based on gene expression profiles. Then, gene-gene interaction networks and pathways related to breast cancer and its subtypes and stages were further identified. The similarity and difference among these subtype-related (and stage-related) networks and pathways were studied, which showed highly specific for subtype Basal-like and Stages IV and V. Finally, gene pairwise interactions associated with breast cancer prognosis were identified by a Cox proportional hazards regression model, and a risk prediction model based on the gene pairs was established, which also performed very well on an independent validation data set. This work will help us to better understand the mechanism underlying the occurrence of breast cancer from the sample-specific network perspective.

SUBMITTER: Zhu K

PROVIDER: S-EPMC7233277 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Personalized analysis of breast cancer using sample-specific networks.

Zhu Ke K Pian Cong C Xiang Qiong Q Liu Xin X Chen Yuanyuan Y

PeerJ 20200515

Breast cancer is a disease with high heterogeneity. Cancer is not usually caused by a single gene, but by multiple genes and their interactions with others and surroundings. Estimating breast cancer-specific gene-gene interaction networks is critical to elucidate the mechanisms of breast cancer from a biological network perspective. In this study, sample-specific gene-gene interaction networks of breast cancer samples were established by using a sample-specific network analysis method based on g ...[more]

PMID: 32461838

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Project description:Histologically similar tumors even from the same anatomical position may still show high variability at molecular level hindering analysis of genome-wide data. Leveling the analysis to a gene regulatory network instead of focusing on single genes has been suggested to overcome the heterogeneity issue although the majority of the network methods require large datasets. Network methods that are able to function at a single sample level are needed to overcome the heterogeneity and sample size issues.We present a novel network method, Differentially Expressed Regulation Analysis (DERA) that integrates expression data to biological network information at a single sample level. The sample-specific networks are subsequently used to discover samples with similar molecular functions by identification of regulations that are shared between samples or are specific for a subgroup.We applied DERA to identify key regulations in triple negative breast cancer (TNBC), which is characterized by lack of estrogen receptor, progesterone receptor and HER2 expression and has poorer prognosis than the other breast cancer subtypes. DERA identified 110 core regulations consisting of 28 disconnected subnetworks for TNBC. These subnetworks are related to oncogenic activity, proliferation, cancer survival, invasiveness and metastasis. Our analysis further revealed 31 regulations specific for TNBC as compared to the other breast cancer subtypes and thus form a basis for understanding TNBC. We also applied DERA to high-grade serous ovarian cancer (HGS-OvCa) data and identified several common regulations between HGS-OvCa and TNBC. The performance of DERA was compared to two pathway analysis methods GSEA and SPIA and our results shows better reproducibility and higher sensitivity in a small sample set.We present a novel method called DERA to identify subnetworks that are similarly active for a group of samples. DERA was applied to breast cancer and ovarian cancer data showing our method is able to identify reliable and potentially important regulations with high reproducibility. R package is available at http://csbi.ltdk.helsinki.fi/pub/czliu/DERA/.

Dataset Information

Personalized analysis of breast cancer using sample-specific networks.

Publications

Personalized analysis of breast cancer using sample-specific networks.

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