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      Deep learning methods for drug response prediction in cancer: Predominant and emerging trends

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          Abstract

          Cancer claims millions of lives yearly worldwide. While many therapies have been made available in recent years, by in large cancer remains unsolved. Exploiting computational predictive models to study and treat cancer holds great promise in improving drug development and personalized design of treatment plans, ultimately suppressing tumors, alleviating suffering, and prolonging lives of patients. A wave of recent papers demonstrates promising results in predicting cancer response to drug treatments while utilizing deep learning methods. These papers investigate diverse data representations, neural network architectures, learning methodologies, and evaluations schemes. However, deciphering promising predominant and emerging trends is difficult due to the variety of explored methods and lack of standardized framework for comparing drug response prediction models. To obtain a comprehensive landscape of deep learning methods, we conducted an extensive search and analysis of deep learning models that predict the response to single drug treatments. A total of 61 deep learning-based models have been curated, and summary plots were generated. Based on the analysis, observable patterns and prevalence of methods have been revealed. This review allows to better understand the current state of the field and identify major challenges and promising solution paths.

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          Most cited references153

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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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            Deep learning.

            Deep learning allows computational models that are composed of multiple processing layers to learn representations of data with multiple levels of abstraction. These methods have dramatically improved the state-of-the-art in speech recognition, visual object recognition, object detection and many other domains such as drug discovery and genomics. Deep learning discovers intricate structure in large data sets by using the backpropagation algorithm to indicate how a machine should change its internal parameters that are used to compute the representation in each layer from the representation in the previous layer. Deep convolutional nets have brought about breakthroughs in processing images, video, speech and audio, whereas recurrent nets have shone light on sequential data such as text and speech.
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              The STRING database in 2021: customizable protein–protein networks, and functional characterization of user-uploaded gene/measurement sets

              Abstract Cellular life depends on a complex web of functional associations between biomolecules. Among these associations, protein–protein interactions are particularly important due to their versatility, specificity and adaptability. The STRING database aims to integrate all known and predicted associations between proteins, including both physical interactions as well as functional associations. To achieve this, STRING collects and scores evidence from a number of sources: (i) automated text mining of the scientific literature, (ii) databases of interaction experiments and annotated complexes/pathways, (iii) computational interaction predictions from co-expression and from conserved genomic context and (iv) systematic transfers of interaction evidence from one organism to another. STRING aims for wide coverage; the upcoming version 11.5 of the resource will contain more than 14 000 organisms. In this update paper, we describe changes to the text-mining system, a new scoring-mode for physical interactions, as well as extensive user interface features for customizing, extending and sharing protein networks. In addition, we describe how to query STRING with genome-wide, experimental data, including the automated detection of enriched functionalities and potential biases in the user's query data. The STRING resource is available online, at https://string-db.org/.
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                Author and article information

                Contributors
                Journal
                Front Med (Lausanne)
                Front Med (Lausanne)
                Front. Med.
                Frontiers in Medicine
                Frontiers Media S.A.
                2296-858X
                15 February 2023
                2023
                : 10
                : 1086097
                Affiliations
                [1] 1Division of Data Science and Learning, Argonne National Laboratory , Lemont, IL, United States
                [2] 2Department of Computer Science, The University of Chicago , Chicago, IL, United States
                Author notes

                Edited by: Mamoru Kato, National Cancer Centre, Japan

                Reviewed by: Amin Emad, McGill University, Canada; Duc-Hau Le, Thuyloi University, Vietnam

                *Correspondence: Alexander Partin ✉ apartin@ 123456anl.gov

                This article was submitted to Precision Medicine, a section of the journal Frontiers in Medicine

                Article
                10.3389/fmed.2023.1086097
                9975164
                36873878
                e6501eaf-c0ad-407e-8374-cb10d909da2c
                Copyright © 2023 Partin, Brettin, Zhu, Narykov, Clyde, Overbeek and Stevens.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 01 November 2022
                : 23 January 2023
                Page count
                Figures: 7, Tables: 1, Equations: 0, References: 155, Pages: 21, Words: 18165
                Funding
                Funded by: U.S. Department of Energy, doi 10.13039/100000015;
                Funded by: National Cancer Research Institute, doi 10.13039/100008667;
                This study has been funded in whole or in part with Federal funding by the NCI-DOE Collaboration established by the U.S. Department of Energy (DOE) and the National Cancer Institute (NCI) of the National Institutes of Health, Cancer Moonshot Task Order No. 75N91019F00134 and under Frederick National Laboratory for Cancer Research Contract 75N91019D00024. This work was performed under the auspices of the U.S. Department of Energy by Argonne National Laboratory under Contract DE-AC02-06-CH11357, Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344, Los Alamos National Laboratory under Contract 89233218CNA000001, and Oak Ridge National Laboratory under Contract DE-AC05-00OR22725.
                Categories
                Medicine
                Review

                deep learning,drug sensitivity,multiomics,neural networks,precision medicine,precision oncology,personalized medicine,drug response prediction

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