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      Network-based machine learning approach to predict immunotherapy response in cancer patients

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          Abstract

          Immune checkpoint inhibitors (ICIs) have substantially improved the survival of cancer patients over the past several years. However, only a minority of patients respond to ICI treatment (~30% in solid tumors), and current ICI-response-associated biomarkers often fail to predict the ICI treatment response. Here, we present a machine learning (ML) framework that leverages network-based analyses to identify ICI treatment biomarkers (NetBio) that can make robust predictions. We curate more than 700 ICI-treated patient samples with clinical outcomes and transcriptomic data, and observe that NetBio-based predictions accurately predict ICI treatment responses in three different cancer types—melanoma, gastric cancer, and bladder cancer. Moreover, the NetBio-based prediction is superior to predictions based on other conventional ICI treatment biomarkers, such as ICI targets or tumor microenvironment-associated markers. This work presents a network-based method to effectively select immunotherapy-response-associated biomarkers that can make robust ML-based predictions for precision oncology.

          Abstract

          Identifying biomarkers for response to immunotherapy in cancer remains challenging. Here, the authors develop an approach based on network biology and machine learning -NetBio- to identify molecular biomarkers of response to immunotherapy across different cancer types and cohorts.

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          Most cited references80

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          Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles

          Although genomewide RNA expression analysis has become a routine tool in biomedical research, extracting biological insight from such information remains a major challenge. Here, we describe a powerful analytical method called Gene Set Enrichment Analysis (GSEA) for interpreting gene expression data. The method derives its power by focusing on gene sets, that is, groups of genes that share common biological function, chromosomal location, or regulation. We demonstrate how GSEA yields insights into several cancer-related data sets, including leukemia and lung cancer. Notably, where single-gene analysis finds little similarity between two independent studies of patient survival in lung cancer, GSEA reveals many biological pathways in common. The GSEA method is embodied in a freely available software package, together with an initial database of 1,325 biologically defined gene sets.
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            Cytoscape: a software environment for integrated models of biomolecular interaction networks.

            Cytoscape is an open source software project for integrating biomolecular interaction networks with high-throughput expression data and other molecular states into a unified conceptual framework. Although applicable to any system of molecular components and interactions, Cytoscape is most powerful when used in conjunction with large databases of protein-protein, protein-DNA, and genetic interactions that are increasingly available for humans and model organisms. Cytoscape's software Core provides basic functionality to layout and query the network; to visually integrate the network with expression profiles, phenotypes, and other molecular states; and to link the network to databases of functional annotations. The Core is extensible through a straightforward plug-in architecture, allowing rapid development of additional computational analyses and features. Several case studies of Cytoscape plug-ins are surveyed, including a search for interaction pathways correlating with changes in gene expression, a study of protein complexes involved in cellular recovery to DNA damage, inference of a combined physical/functional interaction network for Halobacterium, and an interface to detailed stochastic/kinetic gene regulatory models.
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              edgeR: a Bioconductor package for differential expression analysis of digital gene expression data

              Summary: It is expected that emerging digital gene expression (DGE) technologies will overtake microarray technologies in the near future for many functional genomics applications. One of the fundamental data analysis tasks, especially for gene expression studies, involves determining whether there is evidence that counts for a transcript or exon are significantly different across experimental conditions. edgeR is a Bioconductor software package for examining differential expression of replicated count data. An overdispersed Poisson model is used to account for both biological and technical variability. Empirical Bayes methods are used to moderate the degree of overdispersion across transcripts, improving the reliability of inference. The methodology can be used even with the most minimal levels of replication, provided at least one phenotype or experimental condition is replicated. The software may have other applications beyond sequencing data, such as proteome peptide count data. Availability: The package is freely available under the LGPL licence from the Bioconductor web site (http://bioconductor.org). Contact: mrobinson@wehi.edu.au
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                Author and article information

                Contributors
                sukim@postech.ac.kr
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                28 June 2022
                28 June 2022
                2022
                : 13
                : 3703
                Affiliations
                [1 ]GRID grid.49100.3c, ISNI 0000 0001 0742 4007, Department of Life Sciences, , Pohang University of Science and Technology, ; Pohang, 37673 Korea
                [2 ]ImmunoBiome Inc., Pohang, 37666 Korea
                [3 ]GRID grid.15444.30, ISNI 0000 0004 0470 5454, Institute of Convergence Science, , Yonsei University, ; Seoul, 03722 Korea
                Author information
                http://orcid.org/0000-0003-3466-2638
                http://orcid.org/0000-0002-3173-1856
                http://orcid.org/0000-0002-1519-9839
                http://orcid.org/0000-0002-3449-3814
                Article
                31535
                10.1038/s41467-022-31535-6
                9240063
                35764641
                4dae80e0-90ed-45eb-8f16-9de5edd4d18f
                © The Author(s) 2022

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 27 September 2021
                : 22 June 2022
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100002541, Pohang University of Science and Technology (POSTECH);
                Award ID: POSTECHIAN fellowship
                Award Recipient :
                Funded by: Korean National Research Foundation (2021R1A2B5B01001903 and 2020R1A6A1A03047902), Ministry of Oceans and Fisheries (“Omics based on fishery disease control technology development and industrialization” (20150242)), IITP (2019-0-01906, Artificial Intelligence Graduate School Program, POSTECH).
                Categories
                Article
                Custom metadata
                © The Author(s) 2022

                Uncategorized
                cancer immunotherapy,machine learning,bladder cancer,melanoma,gastric cancer
                Uncategorized
                cancer immunotherapy, machine learning, bladder cancer, melanoma, gastric cancer

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