AUTHOR=Yan Haidan , Deng Xusheng , Chen Haifeng , Cheng Jun , He Jun , Guan Qingzhou , Li Meifeng , Xie Jiajing , Xia Jie , Gu Yunyan , Guo Zheng TITLE=Identification of Common and Subtype-Specific Mutated Sub-Pathways for a Cancer JOURNAL=Frontiers in Genetics VOLUME=10 YEAR=2019 URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2019.01228 DOI=10.3389/fgene.2019.01228 ISSN=1664-8021 ABSTRACT=

The heterogeneity of cancer is a big obstacle for cancer diagnosis and treatment. Prioritizing combinations of driver genes that mutate in most patients of a specific cancer or a subtype of this cancer is a promising way to tackle this problem. Here, we developed an empirical algorithm, named PathMG, to identify common and subtype-specific mutated sub-pathways for a cancer. By analyzing mutation data of 408 samples (Lung-data1) for lung cancer, three sub-pathways each covering at least 90% of samples were identified as the common sub-pathways of lung cancer. These sub-pathways were enriched with mutated cancer genes and drug targets and were validated in two independent datasets (Lung-data2 and Lung-data3). Especially, applying PathMG to analyze two major subtypes of lung cancer, lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LSCC), we identified 13 subtype-specific sub-pathways with at least 0.25 mutation frequency difference between LUAD and LSCC samples in Lung-data1, and 12 of the 13 sub-pathways were reproducible in Lung-data2 and Lung-data3. Similar analyses were done for colorectal cancer. Together, PathMG provides us a novel tool to identify potential common and subtype-specific sub-pathways for a cancer, which can provide candidates for cancer diagnoses and sub-pathway targeted treatments.