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      Machine learning in onco-pharmacogenomics: a path to precision medicine with many challenges

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          Abstract

          Over the past two decades, Next-Generation Sequencing (NGS) has revolutionized the approach to cancer research. Applications of NGS include the identification of tumor specific alterations that can influence tumor pathobiology and also impact diagnosis, prognosis and therapeutic options. Pharmacogenomics (PGx) studies the role of inheritance of individual genetic patterns in drug response and has taken advantage of NGS technology as it provides access to high-throughput data that can, however, be difficult to manage. Machine learning (ML) has recently been used in the life sciences to discover hidden patterns from complex NGS data and to solve various PGx problems. In this review, we provide a comprehensive overview of the NGS approaches that can be employed and the different PGx studies implicating the use of NGS data. We also provide an excursus of the ML algorithms that can exert a role as fundamental strategies in the PGx field to improve personalized medicine in cancer.

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          Most cited references243

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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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            Random Forests

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              The 2021 WHO Classification of Tumors of the Central Nervous System: a summary

              The fifth edition of the WHO Classification of Tumors of the Central Nervous System (CNS), published in 2021, is the sixth version of the international standard for the classification of brain and spinal cord tumors. Building on the 2016 updated fourth edition and the work of the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy, the 2021 fifth edition introduces major changes that advance the role of molecular diagnostics in CNS tumor classification. At the same time, it remains wedded to other established approaches to tumor diagnosis such as histology and immunohistochemistry. In doing so, the fifth edition establishes some different approaches to both CNS tumor nomenclature and grading and it emphasizes the importance of integrated diagnoses and layered reports. New tumor types and subtypes are introduced, some based on novel diagnostic technologies such as DNA methylome profiling. The present review summarizes the major general changes in the 2021 fifth edition classification and the specific changes in each taxonomic category. It is hoped that this summary provides an overview to facilitate more in-depth exploration of the entire fifth edition of the WHO Classification of Tumors of the Central Nervous System.
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                Author and article information

                Contributors
                URI : https://loop.frontiersin.org/people/2433479/overviewRole: Role: Role:
                URI : https://loop.frontiersin.org/people/1141390/overviewRole: Role: Role: Role:
                URI : https://loop.frontiersin.org/people/53438/overviewRole: Role: Role: Role:
                URI : https://loop.frontiersin.org/people/1119776/overviewRole: Role: Role: Role: Role:
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                09 January 2024
                2023
                : 14
                : 1260276
                Affiliations
                Experimental and Clinical Pharmacology Unit , Centro di Riferimento Oncologico di Aviano (CRO) , Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) , Aviano, Italy
                Author notes

                Edited by: Shaoqiu Chen, University of Hawaii at Mānoa, United States

                Reviewed by: Luca Cardone, National Research Council (CNR), Italy

                Rui Wang, The First Affiliated Hospital of Xi’an Jiaotong University, China

                *Correspondence: Maurizio Polano, mpolano@ 123456cro.it
                Article
                1260276
                10.3389/fphar.2023.1260276
                10803549
                38264526
                d0c9e9ba-1fe0-4752-8c34-06e7a5453859
                Copyright © 2024 Mondello, Dal Bo, Toffoli and Polano.

                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
                : 17 July 2023
                : 26 December 2023
                Funding
                The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work is founded by the Progetto di Ricerca Finalizzata Regione Friuli Venezia Giulia Anno 2021 LR 13/2021, art. 8, c. 28-30 to GT (CUP J35F21002710002 of Centro di Riferimento Oncologico di Aviano, IRCCS), and by the Italian Ministry of Health (Ricerca Corrente).
                Categories
                Pharmacology
                Review
                Custom metadata
                Pharmacogenetics and Pharmacogenomics

                Pharmacology & Pharmaceutical medicine
                pharmacogenomics,machine learning,omics,targeted therapy,drug toxicity,drug efficacy,drug repurposing

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