title: Incorporating inter-relationships between different levels of genomic data into cancer clinical outcome prediction.
abstract: In order to improve our understanding of cancer and develop multi-layered theoretical models for the underlying mechanism, it is essential to have enhanced understanding of the interactions between multiple levels of genomic data that contribute to tumor formation and progression. Although there exist recent approaches such as a graph-based framework that integrates multi-omics data including copy number alteration, methylation, gene expression, and miRNA data for cancer clinical outcome prediction, most of previous methods treat each genomic data as independent and the possible interplay between them is not explicitly incorporated to the model. However, cancer is dysregulated by multiple levels in the biological system through genomic, epigenomic, transcriptomic, and proteomic level. Thus, genomic features are likely to interact with other genomic features in the different genomic levels. In order to deepen our knowledge, it would be desirable to incorporate such inter-relationship information when integrating multi-omics data for cancer clinical outcome prediction. In this study, we propose a new graph-based framework that integrates not only multi-omics data but inter-relationship between them for better elucidating cancer clinical outcomes. In order to highlight the validity of the proposed framework, serous cystadenocarcinoma data from TCGA was adopted as a pilot task. The proposed model incorporating inter-relationship between different genomic features showed significantly improved performance compared to the model that does not consider inter-relationship when integrating multi-omics data. For the pair between miRNA and gene expression data, the model integrating miRNA, for example, gene expression, and inter-relationship between them with an AUC of 0.8476 (REI) outperformed the model combining miRNA and gene expression data with an AUC of 0.8404. Similar results were also obtained for other pairs between different levels of genomic data. Integration of different levels of data and inter-relationship between them can aid in extracting new biological knowledge by drawing an integrative conclusion from many pieces of information collected from diverse types of genomic data, eventually leading to more effective screening strategies and alternative therapies that may improve outcomes.
authors.affiliation: Seoul National University Biomedical Informatics (SNUBI), Div. of Biomedical Informatics, Seoul National University College of Medicine, Seoul 110799, Republic of Korea; Center for Systems Genomics, Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA, USA. Electronic address: duk27@psu.edu.
authors.forename: Dokyoon
authors.initials: D
authors.lastname: Kim
authors.affiliation: Department of Industrial & Information Systems Engineering, Ajou University, San 5, Wonchun-dong, Yeoungtong-gu, 443-749 Suwon, Republic of Korea. Electronic address: shin@ajou.ac.kr.
authors.forename: Hyunjung
authors.initials: H
authors.lastname: Shin
authors.affiliation: Department of Information and Computer Engineering, Ajou University, Suwon 443-749, Republic of Korea. Electronic address: kasohn@ajou.ac.kr.
authors.forename: Kyung-Ah
authors.initials: KA
authors.lastname: Sohn
authors.affiliation: Center for Systems Genomics, Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA, USA. Electronic address: anurag.verma@psu.edu.
authors.forename: Anurag
authors.initials: A
authors.lastname: Verma
authors.affiliation: Center for Systems Genomics, Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA, USA. Electronic address: marylyn.ritchie@psu.edu.
authors.forename: Marylyn D
authors.initials: MD
authors.lastname: Ritchie
authors.affiliation: Seoul National University Biomedical Informatics (SNUBI), Div. of Biomedical Informatics, Seoul National University College of Medicine, Seoul 110799, Republic of Korea; Systems Biomedical Informatics Research Center, Seoul National University, Seoul 110799, Republic of Korea. Electronic address: juhan@snu.ac.kr.
authors.forename: Ju Han
authors.initials: JH
authors.lastname: Kim
mesh_terms: D003536:Cystadenocarcinoma / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D005260:Female; D020869:Gene Expression Profiling; D023281:Genomics / Q000379:methods*; D006801:Humans; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D057285:Precision Medicine; D011379:Prognosis; D016896:Treatment Outcome
keywords: Clinical outcome prediction; Data integration; Inter-relationship; Multi-omics data; Ovarian cancer; TCGA