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      Improving cancer driver gene identification using multi-task learning on graph convolutional network

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          Abstract

          Cancer is thought to be caused by the accumulation of driver genetic mutations. Therefore, identifying cancer driver genes plays a crucial role in understanding the molecular mechanism of cancer and developing precision therapies and biomarkers. In this work, we propose a Multi-Task learning method, called MTGCN, based on the Graph Convolutional Network to identify cancer driver genes. First, we augment gene features by introducing their features on the protein-protein interaction (PPI) network. After that, the multi-task learning framework propagates and aggregates nodes and graph features from input to next layer to learn node embedding features, simultaneously optimizing the node prediction task and the link prediction task. Finally, we use a Bayesian task weight learner to balance the two tasks automatically. The outputs of MTGCN assign each gene a probability of being a cancer driver gene. Our method and the other four existing methods are applied to predict cancer drivers for pan-cancer and some single cancer types. The experimental results show that our model shows outstanding performance compared with the state-of-the-art methods in terms of the area under the Receiver Operating Characteristic (ROC) curves and the area under the precision-recall curves.

          The MTGCN is freely available via https://github.com/weiba/MTGCN.

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          Most cited references46

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          Signatures of mutational processes in human cancer

          All cancers are caused by somatic mutations. However, understanding of the biological processes generating these mutations is limited. The catalogue of somatic mutations from a cancer genome bears the signatures of the mutational processes that have been operative. Here, we analysed 4,938,362 mutations from 7,042 cancers and extracted more than 20 distinct mutational signatures. Some are present in many cancer types, notably a signature attributed to the APOBEC family of cytidine deaminases, whereas others are confined to a single class. Certain signatures are associated with age of the patient at cancer diagnosis, known mutagenic exposures or defects in DNA maintenance, but many are of cryptic origin. In addition to these genome-wide mutational signatures, hypermutation localized to small genomic regions, kataegis, is found in many cancer types. The results reveal the diversity of mutational processes underlying the development of cancer with potential implications for understanding of cancer etiology, prevention and therapy.
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            Is Open Access

            The Cancer Genome Atlas Pan-Cancer analysis project.

            The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile.
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              Adjusting batch effects in microarray expression data using empirical Bayes methods.

              Non-biological experimental variation or "batch effects" are commonly observed across multiple batches of microarray experiments, often rendering the task of combining data from these batches difficult. The ability to combine microarray data sets is advantageous to researchers to increase statistical power to detect biological phenomena from studies where logistical considerations restrict sample size or in studies that require the sequential hybridization of arrays. In general, it is inappropriate to combine data sets without adjusting for batch effects. Methods have been proposed to filter batch effects from data, but these are often complicated and require large batch sizes ( > 25) to implement. Because the majority of microarray studies are conducted using much smaller sample sizes, existing methods are not sufficient. We propose parametric and non-parametric empirical Bayes frameworks for adjusting data for batch effects that is robust to outliers in small sample sizes and performs comparable to existing methods for large samples. We illustrate our methods using two example data sets and show that our methods are justifiable, easy to apply, and useful in practice. Software for our method is freely available at: http://biosun1.harvard.edu/complab/batch/.
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                Author and article information

                Contributors
                Journal
                Briefings in Bioinformatics
                Oxford University Press (OUP)
                1467-5463
                1477-4054
                January 2022
                January 17 2022
                January 2022
                January 17 2022
                October 13 2021
                : 23
                : 1
                Affiliations
                [1 ]Faculty of Information Engineering and Automation, Kunming University of Science and Technology, Kunming, Yunnan 650500, P. R. China
                [2 ]Technology Application Key Lab of Yunnan Province, Kunming University of Science and Technology, Kunming, Yunnan 650500, P. R. China
                Article
                10.1093/bib/bbab432
                34643232
                294378e1-2613-423f-ab95-69fa7565bd30
                © 2021

                https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model

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