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An open science study of ageing in companion dogs (vol 602, g 51, 2022)

NATURE 2022年第7924期608卷 E33-E33页

作者： Creevy, Kate E. Akey, Joshua M. Kaeberlein, Matt Promislow, Daniel E. L. Department of Small Animal Clinical Sciences Texas A&M University College of Veterinary Medicine & Biomedical Sciences College Station TX USA Lewis-Sigler Institute for Integrative Genomics Princeton University Princeton NJ USA Department of Laboratory Medicine and Pathology University of Washington School of Medicine Seattle WA USA Department of Biology University of Washington Seattle WA USA Institute for Stem Cell and Regenerative Medicine University of Washington Seattle WA USA Department of Clinical Microbiology and Immunology Sackler Faculty of Medicine Tel Aviv University Tel Aviv Israel Blavatnik School of Computer Science Tel Aviv University Tel Aviv Israel Santa Fe Institute Santa Fe NM USA Cornell Veterinary Biobank College of Veterinary Medicine Cornell University Ithaca NY USA Department of Sociology University of Washington Seattle WA USA Center for Studies in Demography and Ecology Seattle WA USA Department of Small Animal Medicine and Surgery University of Georgia College of Veterinary Medicine Athens GA USA Department of Veterinary Physiology and Pharmacology Texas A&M University College of Veterinary Medicine & Biomedical Sciences College Station TX USA Department of Family Medicine University of Washington Seattle WA USA Department of Epidemiology University of Washington Seattle WA USA Department of Global Health University of Washington Seattle WA USA Epidemiology Program Fred Hutchinson Cancer Research Center Seattle WA USA Department of Veterinary Pathobiology Texas A&M University College of Veterinary Medicine & Biomedical Sciences College Station TX USA Bioinformatics and Integrative Biology University of Massachusetts Chan Medical School Worcester MA USA Broad Institute of MIT and Harvard Cambridge MA USA Department of Biostatistics University of Washington Seattle WA USA Division of Public Health Sciences Fred Hutchinson Cancer Research Center Seattle WA USA Department of Population Health Sciences Vir

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The evolutionary history of 2,658 cancers (vol 578, pg 122, 2020)

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NATURE 2023年第7948期614卷 E42-E42页

作者： Gerstung, Moritz Jolly, Clemency Leshchiner, Ignaty Dentro, Stefan C. Gonzalez, Santiago Rosebrock, Daniel Mitchell, Thomas J. Rubanova, Yulia Anur, Pavana Yu, Kaixian Tarabichi, Maxime Deshwar, Amit Wintersinger, Jeff Kleinheinz, Kortine Vazquez-Garcia, Ignacio Haase, Kerstin Jerman, Lara Sengupta, Subhajit Macintyre, Geoff Malikic, Salem Donmez, Nilgun Livitz, Dimitri G. Cmero, Marek Demeulemeester, Jonas Schumacher, Steven Fan, Yu Yao, Xiaotong Lee, Juhee Schlesner, Matthias Boutros, Paul C. Bowtell, David D. Zhu, Hongtu Getz, Gad Imielinski, Marcin Beroukhim, Rameen Sahinalp, S. Cenk Ji, Yuan Peifer, Martin Markowetz, Florian Mustonen, Ville Yuan, Ke Wang, Wenyi Morris, Quaid D. Spellman, Paul T. Wedge, David C. Van Loo, Peter European Molecular Biology Laboratory European Bioinformatics Institute (EMBL-EBI) Cambridge UK European Molecular Biology Laboratory Genome Biology Unit Heidelberg Germany Wellcome Sanger Institute Cambridge UK Genome Biology Unit European Molecular Biology Laboratory (EMBL) Heidelberg Germany University of Ljubljana Ljubljana Slovenia The Francis Crick Institute London UK Big Data Institute University of Oxford Oxford UK Wellcome Sanger Institute Wellcome Genome Campus Hinxton UK Big Data Institute Li Ka Shing Centre University of Oxford Oxford UK University of Cambridge Cambridge UK Cambridge University Hospitals NHS Foundation Trust Cambridge UK Department of Applied Mathematics and Theoretical Physics Centre for Mathematical Sciences University of Cambridge Cambridge UK Department of Epidemiology and Biostatistics Memorial Sloan Kettering Cancer Center New York NY USA Department of Statistics Columbia University New York NY USA Department of Haematology University of Cambridge Cambridge UK University of Leuven Leuven Belgium Broad Institute of MIT and Harvard Cambridge MA USA Center for Cancer Research Massachusetts General Hospital Charlestown MA USA Department of Pathology Massachusetts General Hospital Boston MA USA Harvard Medical School Boston MA USA Center for Cancer Research Massachusetts General Hospital Boston MA USA Dana-Farber Cancer Institute Boston MA USA Department of Medical Oncology Dana-Farber Cancer Institute Boston MA USA Department of Cancer Biology Dana-Farber Cancer Institute Boston MA USA Oxford NIHR Biomedical Research Centre Oxford UK Oxford NIHR Biomedical Research Centre University of Oxford Oxford UK University of Toronto Toronto Ontario Canada Vector Institute Toronto Ontario Canada Vector Institute Toronto ON Canada Department of Computer Science University of Toronto Toronto ON Canada Ontario Institute for Cancer Research Toronto Ontario Canada University of California Los Angeles

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scTenifoldXct: A semi-supervised method for predicting cell-cell interactions and mapping cellular communication graphs

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Cell systems 2023年第4期14卷 302-311.e4页

作者： Yongjian Yang Guanxun Li Yan Zhong Qian Xu Yu-Te Lin Cristhian Roman-Vicharra Robert S Chapkin James J Cai Department of Electrical and Computer Engineering Texas A&M University College Station TX 77843 USA. Department of Statistics Texas A&M University College Station TX 77843 USA. Key Laboratory of Advanced Theory and Application in Statistics and Data Science-MOE School of Statistics East China Normal University 3663 North Zhongshan Road Shanghai 200062 China. Department of Veterinary Integrative Biosciences Texas A&M University College Station TX 77843 USA. Graduate Institute of Biomedical Electronics and Bioinformatics National Taiwan University Taipei Taiwan. Department of Nutrition and the Program in Integrative Nutrition & Complex Diseases Texas A&M University College Station TX 77843 USA. Electronic address: r-chapkin@tamu.edu. Department of Electrical and Computer Engineering Texas A&M University College Station TX 77843 USA Department of Veterinary Integrative Biosciences Texas A&M University College Station TX 77843 USA Interdisciplinary Program of Genetics Texas A&M University College Station TX 77843 USA. Electronic address: jcai@tamu.edu.

We present scTenifoldXct, a semi-supervised computational tool for detecting ligand-receptor (LR)-mediated cell-cell interactions and mapping cellular communication graphs. Our method is based on manifold alignment, using LR pairs as inter-data correspondences to embed ligand and receptor genes expressed in interacting cells into a unified latent space. Neural networks are employed to minimize the distance between corresponding genes while preserving the structure of gene regression networks. We apply scTenifoldXct to real datasets for testing and demonstrate that our method detects interactions with high consistency compared with other methods. More importantly, scTenifoldXct uncovers weak but biologically relevant interactions overlooked by other methods. We also demonstrate how scTenifoldXct can be used to compare different samples, such as healthy vs. diseased and wild type vs. knockout, to identify differential interactions, thereby revealing functional implications associated with changes in cellular communication status.

关键词： cell-cell interaction cellular communication gene regression network machine learning manifold alignment neural networks scRNA-seq single-cell RNA sequencing

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Assessing the Potential of GPT-4 to Annotate Medical Notes Across Different Languages and Countries: A Model Evaluation Study

SSRN

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SSRN 2024年

作者： Saad Menezes, Maria Clara Hoffman, Alexander F. Tan, Amelia L.M. Nalbandyan, Mariné Omenn, Gilbert S. Mazzotti, Diego R. Hernández-Arango, Alejandro Visweswaran, Shyam Venkatesh, Shruthi Mandl, Kenneth D. Bourgeois, Florence T. Lee, James W.K. Makmur, Andrew Hanauer, David A. Semanik, Michael G. Kerivan, Lauren T. Hill, Terra Forero, Julian Restrepo Castro, Carlos Andrés C.R. Vigna, Matteo Ceriana, Piero Abu-El-rub, Noor Avillach, Paul Bellazzi, Riccardo Callaci, Thomas Gutiérrez-Sacristán, Alba Malovini, Alberto Mathew, Jomol P. Morris, Michele Murthy, Venkatesh Parimbelli, Enea Patel, Lav P. Sáez, Carlos Samayamuthu, Malarkodi Jebathilagam Thompson, Jeffrey A. Tibollo, Valentina Xia, Zongqi Kohane, Isaac S. Harvard Medical School Department of Biomedical Informatics 10 Shattuck Street BostonMA02115 United States School of Medicine and Public Health University of Wisconsin-Madison Office of Informatics and Information Technology 750 Highland Ave MadisonWI53705 United States University of Michigan Department of Computational Medicine & Bioinformatics Internal Medicine Human Genetics Environmental Health 100 Washtenaw Avenue Ann ArborMI48109 United States University of Kansas Medical Center Division of Medical Informatics Division of Pulmonary Critical Care and Sleep Medicine Department of Internal Medicine 3901 Rainbow Blvd Kansas CityKS66160 United States University of Antioquia Hospital Alma Máter de Antioquia Department of Internal Medicine Calle 64 N°51 D - 154 Medellín Colombia University of Pittsburgh Department of Biomedical Informatics 5607 Baum Blvd PittsburghPA15206 United States University of Pittsburgh Department of Neurology 3501 5th Avenue PittsburghPA15206 United States Boston Children's Hospital Computational Health Informatics Program 300 Longwood Avenue BostonMA02115 United States Boston Children's Hospital Department of Pediatrics 300 Longwood Avenue BostonMA02115 United States National University Health System Department of Surgery 1E Kent Ridge Rd Singapore119228 Singapore National University Health System Department of Diagnostic Imaging 1E Kent Ridge Rd Singapore119228 Singapore University of Michigan Department of Learning Health Sciences NCRC 100 2800 Plymouth Road Ann ArborMI48109 United States University of Kansas Medical Center Department of Surgery 3901 Rainbow Blvd Kansas CityKS66160 United States Istituti Clinici Scientifici Maugeri IRCCS Respiratory rehabilitation unit Via Maugeri 10 Pavia27100 Italy University of Kansas Medical Center 3901 Rainbow Blvd Kansas CityKS66160 United States University of Pavia Department of Electrical Computer and Biomedical Engineering via Ferrata 5 Pavia2710

Background: Physicians invest hours creating patient notes, which are rich in information but difficult for computers to analyze due to their unstructured format. GPT-4 reshaped our ability to process text, yet it is unknown how well this model can handle medical notes. This project aims to compare GPT-4’s ability to annotate medical notes against experienced physicians across three different languages at multiple institutions and countries. Methods: This study included eight sites from four countries - the United States, Colombia, Singapore, and Italy. Each site contributed seven de-identified notes (admission, progress, or consult) from hospitalized patients. GPT-4 assessed each note by answering 14 questions, including demographic information, clinical judgments, data quality, and patients’ eligibility for a hypothetical study enrollment. For validation, two physicians from each site independently evaluated GPT-4's responses. Findings: Overall, 56 medical notes, written in English, Italian, and Spanish, were analyzed. A total of 784 responses from GPT-4 were generated. Both physicians agreed with GPT-4’s response 79% of the time (622/784, 95%CI 76-82%). Only one of the two physicians agreed with GPT-4’s response 10% of the time (82/784, 95%CI 8-13%). Neither physician agreed with GPT-4’s response 10% of the time (80/784, 95%CI 8-13%). Both physicians agreed with GPT-4 more often in notes written in Spanish and Italian than in English, with agreement rates of 88% (86/98, 95%CI 79-93%), 84% (82/98, 95%CI 75-90%), and 77% (454/588, 95%CI 74-80%), respectively. Hallucinations were rare (10/784, 95%CI 0-2%). GPT-4 correctly selected patients for a hypothetical study enrollment based on three criteria 90% of the time (95%CI 81-98%). Interpretation: The findings indicate that GPT-4 annotations demonstrated a high agreement rate with physicians across all languages. We also demonstrate GPT-4's potential to assist in patient selection for studies. Funding: None. Declarati

关键词： Medical computing

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Reference Data Based Insights Expand Understanding of Human Metabolomes

SSRN

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SSRN 2020年

作者： Gauglitz, Julia M. Bittremieux, Wout Williams, Candace L. Weldon, Kelly C. Panitchpakdi, Morgan Di Ottavio, Francesca Aceves, Christine M. Brown, Elizabeth Sikora, Nicole C. Jarmusch, Alan K. Martino, Cameron Tripathi, Anupriya Sayyari, Erfan Shaffer, Justin P. Coras, Roxana Vargas, Fernando DeRight Goldasich, Lindsay Schwartz, Tara Bryant, MacKenzie Humphrey, Gregory Johnson, Abigail J. Spengler, Katharina Belda-Ferre, Pedro Diaz, Edgar McDonald, Daniel Zhu, Qiyun Nguyen, Dominic S. Elijah, Emmanuel O. Wang, Mingxun Marotz, Clarisse Sprecher, Kate E. Robles, Daniela Vargas Withrow, Dana Ackermann, Gail Herrera, Lourdes Bradford, Barry J. Marques, Lucas Maciel Mauriz Amaral, Juliano Geraldo Silva, Rodrigo Moreira Veras, Flávio Protaso Cunha, Thiago Mattar Oliveira, Rene Donizeti Ribeiro Louzada-Junior, Paulo Mills, Robert H. Galasko, Douglas Dulai, Parambir S. Wittenberg, Curt Gonzalez, David J. Terkeltaub, Robert Doty, Megan M. Kim, Jae H. Rhee, Kyung E. Beauchamp-Walters, Julia Wright, Kenneth P. Dominguez-Bello, Maria Gloria Manary, Mark Oliveira, Michelli F. Boland, Brigid S. Lopes, Norberto Peporine Guma, Monica Swafford, Austin D. Dutton, Rachel J. Knight, Rob Dorrestein, Pieter C. Collaborative Mass Spectrometry Innovation Center University of California San Diego San DiegoCA92093 United States Skaggs School of Pharmacy and Pharmaceutical Sciences University of California San Diego San DiegoCA92093 United States Department of Computer Science University of Antwerp Antwerpen2020 Belgium Reproductive Sciences Institute for Conservation Research San Diego Zoo Global EscondidoCA92027 United States Center for Microbiome Innovation Joan and Irwin Jacobs School of Engineering University of California San Diego San DiegoCA92093 United States Division of Biological Sciences University of California San Diego San DiegoCA92093 United States Department of Pediatrics School of Medicine University of California San Diego San DiegoCA92093 United States Bioinformatics and Systems Biology Program University of California San Diego San DiegoCA92093 United States Division of Rheumatology Allergy & Immunology Department of Medicine University of California San Diego San DiegoCA92093 United States BioTechnology Institute University of Minnesota Saint PaulMN55108 United States Department of Integrative Physiology University of Colorado Boulder BoulderCO80309 United States Department of Population Health Sciences University of Wisconsin-Madison MadisonWI53726 United States Servicio Autónomo Centro Amazónico de Investigación y Control de Enfermedades Tropicales Simón Bolívar Amazonas Puerto Ayacucho7101 Venezuela Department of Pediatrics Wake Forest School of Medicine Winston-SalemNC27101 United States Department of Animal Science Michigan State University East LansingMI48824 United States Department of Pharmacology School of Medicine of Ribeirao Preto Center of Research in Inflammatory Diseases University of Sao Paulo SP Ribeirao PretoCEP 14049-900 - Brazil Multidisciplinary Health Institute Federal University of Bahia BA Vitória da Conquista45029094 Brazil NPPNS Department of Biomolecular Sciences School of Pharmaceutica

The human metabolome has remained largely unknown, with most studies annotating ~10% of features. In nucleic acid sequencing, annotating transcripts by source has proven essential for understanding gene function. Here we generalize this concept to stool, plasma, urine and other human metabolomes, discovering that food-based annotations increase the interpreted fraction of molecular features 7-fold, providing a general framework for expanding the interpretability of human metabolomic "dark matter." © 2020, The Authors. All rights reserved.

关键词： Nucleic acids

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Author Correction: A B-ARR-mediated cytokinin transcriptional network directs hormone cross-regulation and shoot development

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Nature communications 2018年第1期9卷 2075页

作者： Mingtang Xie Hongyu Chen Ling Huang Ryan C O'Neil Maxim N Shokhirev Joseph R Ecker Plant Biology Laboratory and Genomic Analysis Laboratory The Salk Institute for Biological Studies La Jolla CA 92037 USA. Howard Hughes Medical Institute The Salk Institute for Biological Studies La Jolla CA 92037 USA. Department of Computer Science Dartmouth College Hanover NH 03755 USA. The Razavi Newman Integrative Genomics and Bioinformatics Core Facility The Salk Institute for Biological Studies La Jolla CA 92037 USA. Bioinformatics Program University of California at San Diego La Jolla CA 92093 USA. Plant Biology Laboratory and Genomic Analysis Laboratory The Salk Institute for Biological Studies La Jolla CA 92037 USA. ecker@salk.edu. Howard Hughes Medical Institute The Salk Institute for Biological Studies La Jolla CA 92037 USA. ecker@salk.edu.

The original version of this Article contained an error in Fig. 3. Panel b was inadvertently duplicated and the correct panel c was originally omitted. This error has been corrected in both the PDF and HTML versions o...

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Author Correction: Predicting the efficiency of prime editing guide RNAs in human cells

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Nature biotechnology 2024年第3期42卷 529页

作者： Hui Kwon Kim Goosang Yu Jinman Park Seonwoo Min Sungtae Lee Sungroh Yoon Hyongbum Henry Kim Department of Pharmacology Yonsei University College of Medicine Seoul Republic of Korea. Brain Korea 21 Plus Project for Medical Sciences Yonsei University College of Medicine Seoul Republic of Korea. Center for Nanomedicine Institute for Basic Science (IBS) Seoul Republic of Korea. Graduate Program of Nano Biomedical Engineering (NanoBME) Advanced Science Institute Yonsei University Seoul Republic of Korea. Electrical and Computer Engineering Seoul National University Seoul Republic of Korea. Interdisciplinary Program in Bioinformatics Seoul National University Seoul Republic of Korea. Graduate School of Data Science Seoul National University Seoul Republic of Korea. Department of Pharmacology Yonsei University College of Medicine Seoul Republic of Korea. hkim1@yuhs.ac. Brain Korea 21 Plus Project for Medical Sciences Yonsei University College of Medicine Seoul Republic of Korea. hkim1@yuhs.ac. Center for Nanomedicine Institute for Basic Science (IBS) Seoul Republic of Korea. hkim1@yuhs.ac. Graduate Program of Nano Biomedical Engineering (NanoBME) Advanced Science Institute Yonsei University Seoul Republic of Korea. hkim1@yuhs.ac. Severance Biomedical Science Institute Yonsei University College of Medicine Seoul Republic of Korea. hkim1@yuhs.ac. Graduate Program of NanoScience and Technology Yonsei University Seoul Republic of Korea. hkim1@yuhs.ac.

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Automatic Extraction of Medication Mentions from Tweets-Overview of the BioCreative VII Shared Task 3 Competition

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Database : the journal of biological databases and curation 2023年第2023期2023卷 baac108页

作者： Davy Weissenbacher Karen O'Connor Siddharth Rawal Yu Zhang Richard Tzong-Han Tsai Timothy Miller Dongfang Xu Carol Anderson Bo Liu Qing Han Jinfeng Zhang Igor Kulev Berkay Köprü Raul Rodriguez-Esteban Elif Ozkirimli Ammer Ayach Roland Roller Stephen Piccolo Peijin Han V G Vinod Vydiswaran Ramya Tekumalla Juan M Banda Parsa Bagherzadeh Sabine Bergler João F Silva Tiago Almeida Paloma Martinez Renzo Rivera-Zavala Chen-Kai Wang Hong-Jie Dai Luis Alberto Robles Hernandez Graciela Gonzalez-Hernandez Department of Computational Biomedicine Cedars-Sinai Medical Center Los Angeles CA USA. DBEI The Perelman School of Medicine University of Pennsylvania Philadelphia PA USA. Department of Computer Science and Information Engineering National Central University No. 300 Zhongda Rd Zhongli District Taoyuan 320 Taiwan. IoX Center National Taiwan University Da'an District Section 4 Roosevelt Rd No. 1 Barry Lam Hall Taipei 106 Taiwan. Research Center for Humanities and Social Sciences Academia Sinica No. 128 Section 2 Academia Rd Nangang District Taipei 115 Taiwan. Computational Health Informatics Program Boston Children's Hospital Boston MA USA. Department of Pediatrics Harvard Medical School Boston MA USA. NVIDIA Santa Clara CA USA. Department of Statistics Florida State University Tallahassee FL USA. Data and Analytics Chapter F. Hoffmann-La Roche Ltd Switzerland. Pharmaceutical Research and Early Development Roche Innovation Center Basel Switzerland. Speech and Language Technology Lab DFKI Berlin Germany. Department of Biology Brigham Young University Provo UT USA. Department of Computational Medicine and Bioinformatics Medical School University of Michigan Ann Arbor MI USA. Department of Learning Health Sciences Medical School University of Michigan Ann Arbor MI USA. School of Information University of Michigan Ann Arbor MI USA. Department of Computer Science Georgia State University Atlanta GA USA. CLaC Labs Concordia University Montreal Canada. DETI Institute of Electronics and Informatics Engineering of Aveiro University of Aveiro Portugal. Department of Computation University of A Coruña Spain. Computer Science and Engineering Department Universidad Carlos III de Madrid Madrid Spain. Big Data Laboratory Chunghwa Telecom Laboratories Taoyuan Taiwan. Department of Computer Science National Yang Ming Chiao Tung University Hsinchu Taiwan. Department of Electrical Engineering College of Electrical Engineering and Computer Sci

This study presents the outcomes of the shared task competition BioCreative VII (Task 3) focusing on the extraction of medication names from a Twitter user's publicly available tweets (the user's 'timeline'). In general, detecting health-related tweets is notoriously challenging for natural language processing tools. The main challenge, aside from the informality of the language used, is that people tweet about any and all topics, and most of their tweets are not related to health. Thus, finding those tweets in a user's timeline that mention specific health-related concepts such as medications requires addressing extreme imbalance. Task 3 called for detecting tweets in a user's timeline that mentions a medication name and, for each detected mention, extracting its span. The organizers made available a corpus consisting of 182 049 tweets publicly posted by 212 Twitter users with all medication mentions manually annotated. The corpus exhibits the natural distribution of positive tweets, with only 442 tweets (0.2%) mentioning a medication. This task was an opportunity for participants to evaluate methods that are robust to class imbalance beyond the simple lexical match. A total of 65 teams registered, and 16 teams submitted a system run. This study summarizes the corpus created by the organizers and the approaches taken by the participating teams for this challenge. The corpus is freely available at https://***/tasks/biocreative-vii/track-3/. The methods and the results of the competing systems are analyzed with a focus on the approaches taken for learning from class-imbalanced data.

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Author Correction: A B-ARR-mediated cytokinin transcriptional network directs hormone cross-regulation and shoot development

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Nature communications 2023年第1期14卷 5988页

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Perspective on recent developments and challenges in regulatory and systems genomics

arXiv

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arXiv 2024年

作者： Zeiltinger, Julia Roy, Sushmita Ay, Ferhat Mathelier, Anthony Medina-Rivera, Alejandra Mahony, Shaun Sinha, Saurabh Ernst, Jason Stowers Institute for Medical Research Kansas CityMO64112 United States Department of Pathology & Laboratory Medicine The University of Kansas Medical Center Kansas CityKS66160 United States Department of Biostatistics and Medical Informatics University of Wisconsin-Madison Madison53715 United States Wisconsin Institute for Discovery University of Wisconsin-Madison Madison53715 United States Centers for Autoimmunity Inflammation and Cancer Immunotherapy La Jolla Institute for Immunology La Jolla CA United States Bioinformatics and Systems Biology Program University of California La Jolla San DiegoCA United States Department of Pediatrics University of California La Jolla San DiegoCA United States Nordic EMBL Partnership University of Oslo Oslo0318 Norway Department of Medical Genetics Institute of Clinical Medicine University of Oslo Oslo University Hospital Oslo Norway Department of Pharmacy University of Oslo Oslo Norway Laboratorio Internacional de Investigación sobre el Genoma Humano Universidad Nacional Autónoma de México Campus Juriquilla Blvd. Juriquilla 3001 Santiago de Querétaro76230 Mexico Center for Eukaryotic Gene Regulation Department of Biochemistry and Molecular Biology The Pennsylvania State University University ParkPA16802 United States Walter H. Coulter Department of Biomedical Engineering Georgia Institute of Technology AtlantaGA United States H. Milton Stewart School of Industrial and Systems Engineering Georgia Institute of Technology AtlantaGA United States Department of Biological Chemistry University of California Los Angeles Los AngelesCA90095 United States Computer Science Department University of California Los Angeles Los AngelesCA90095 United States Department of Computational Medicine University of California Los Angeles Los AngelesCA90095 United States Eli and Edythe Broad Center of Regenerative Medicine Stem Cell Research University of California Los Angeles Los AngelesCA90095 United States

Predicting how genetic variation affects phenotypic outcomes at the organismal, cellular, and molecular levels requires deciphering the cis-regulatory code, the sequence rules by which non-coding regions regulate genes. In this perspective, we discuss recent computational progress and challenges towards solving this fundamental problem. We describe how cis-regulatory elements are mapped and how their sequence rules can be learned and interpreted with sequence-to-function neural networks, with the goal of identifying genetic variants in human disease. We also discuss how studies of the 3D chromatin organization could help identifying long-range regulatory effects and how current methods for mapping gene regulatory networks could better describe biological processes. We point out current gaps in knowledge along with technical limitations and benchmarking challenges of computational methods. Finally, we discuss newly emerging technologies, such as spatial transcriptomics, and outline strategies for creating a more general model of the cis-regulatory code that is more broadly applicable across cell types and individuals. © 2024, CC BY-NC-SA.

关键词： Molecular docking

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