Genome Medicine最新文献

{"title":"Genomic insights into the plasmidome of non-tuberculous mycobacteria.","authors":"Margo Diricks, Florian P Maurer, Viola Dreyer, Ivan Barilar, Christian Utpatel, Matthias Merker, Nils Wetzstein, Stefan Niemann","doi":"10.1186/s13073-025-01443-7","DOIUrl":"10.1186/s13073-025-01443-7","url":null,"abstract":"<p><strong>Background: </strong>Non-tuberculous mycobacteria (NTM) are a diverse group of environmental bacteria that are increasingly associated with human infections and difficult to treat. Plasmids, which might carry resistance and virulence factors, remain largely unexplored in NTM.</p><p><strong>Methods: </strong>We used publicly available complete genome sequence data of 328 NTM isolates belonging to 125 species to study gene content, genomic diversity, and clusters of 196 annotated NTM plasmids. Furthermore, we analyzed 3755 draft genome assemblies from over 200 NTM species and 5415 short-read sequence datasets from six clinically relevant NTM species or complexes including M. abscessus, M. avium complex, M. ulcerans complex and M. kansasii complex, for the presence of these plasmids.</p><p><strong>Results: </strong>Between one and five plasmids were present in approximately one-third of the complete NTM genomes. The annotated plasmids varied widely in length (most between 10 and 400 kbp) and gene content, with many genes having an unknown function. Predicted gene functions primarily involved plasmid replication, segregation, maintenance, and mobility. Only a few plasmids contained predicted genes that are known to confer resistance to antibiotics commonly used to treat NTM infections. Out of 196 annotated plasmid sequences, 116 could be grouped into 31 clusters of closely related sequences, and about one-third were found across multiple NTM species. Among clinically relevant NTM, the presence of NTM plasmids showed significant variation between species, within (sub)species, and even among strains within (sub)lineages, such as dominant circulating clones of Mycobacterium abscessus.</p><p><strong>Conclusions: </strong>Our analysis demonstrates that plasmids are a diverse and heterogeneously distributed feature in NTM bacteria. The frequent occurrence of closely related putative plasmid sequences across different NTM species suggests they may play a significant role in NTM evolution through horizontal gene transfer at least in some groups of NTM. However, further in vitro investigations and access to more complete genomes are necessary to validate our findings, elucidate gene functions, identify novel plasmids, and comprehensively assess the role of plasmids in NTM.</p>","PeriodicalId":12645,"journal":{"name":"Genome Medicine","volume":"17 1","pages":"19"},"PeriodicalIF":10.4,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11877719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural variants linked to Alzheimer's disease and other common age-related clinical and neuropathologic traits.","authors":"Ricardo A Vialle, Katia de Paiva Lopes, Yan Li, Bernard Ng, Julie A Schneider, Aron S Buchman, Yanling Wang, Jose M Farfel, Lisa L Barnes, Aliza P Wingo, Thomas S Wingo, Nicholas T Seyfried, Philip L De Jager, Chris Gaiteri, Shinya Tasaki, David A Bennett","doi":"10.1186/s13073-025-01444-6","DOIUrl":"10.1186/s13073-025-01444-6","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is a complex neurodegenerative disorder with substantial genetic influence. While genome-wide association studies (GWAS) have identified numerous risk loci for late-onset AD (LOAD), the functional mechanisms underlying most of these associations remain unresolved. Large genomic rearrangements, known as structural variants (SVs), represent a promising avenue for elucidating such mechanisms within some of these loci.</p><p><strong>Methods: </strong>By leveraging data from two ongoing cohort studies of aging and dementia, the Religious Orders Study and Rush Memory and Aging Project (ROS/MAP), we performed genome-wide association analysis testing 20,205 common SVs from 1088 participants with whole genome sequencing (WGS) data. A range of Alzheimer's disease and other common age-related clinical and neuropathologic traits were examined.</p><p><strong>Results: </strong>First, we mapped SVs across 81 AD risk loci and discovered 22 SVs in linkage disequilibrium (LD) with GWAS lead variants and directly associated with the phenotypes tested. The strongest association was a deletion of an Alu element in the 3'UTR of the TMEM106B gene, in high LD with the respective AD GWAS locus and associated with multiple AD and AD-related disorders (ADRD) phenotypes, including tangles density, TDP-43, and cognitive resilience. The deletion of this element was also linked to lower TMEM106B protein abundance. We also found a 22-kb deletion associated with depression in ROS/MAP and bearing similar association patterns as GWAS SNPs at the IQCK locus. In addition, we leveraged our catalog of SV-GWAS to replicate and characterize independent findings in SV-based GWAS for AD and five other neurodegenerative diseases. Among these findings, we highlight the replication of genome-wide significant SVs for progressive supranuclear palsy (PSP), including markers for the 17q21.31 MAPT locus inversion and a 1483-bp deletion at the CYP2A13 locus, along with other suggestive associations, such as a 994-bp duplication in the LMNTD1 locus, suggestively linked to AD and a 3958-bp deletion at the DOCK5 locus linked to Lewy body disease (LBD) (P = 3.36 × 10^-4).</p><p><strong>Conclusions: </strong>While still limited in sample size, this study highlights the utility of including analysis of SVs for elucidating mechanisms underlying GWAS loci and provides a valuable resource for the characterization of the effects of SVs in neurodegenerative disease pathogenesis.</p>","PeriodicalId":12645,"journal":{"name":"Genome Medicine","volume":"17 1","pages":"20"},"PeriodicalIF":10.4,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881306/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"STModule: identifying tissue modules to uncover spatial components and characteristics of transcriptomic landscapes.","authors":"Ran Wang, Yan Qian, Xiaojing Guo, Fangda Song, Zhiqiang Xiong, Shirong Cai, Xiuwu Bian, Man Hon Wong, Qin Cao, Lixin Cheng, Gang Lu, Kwong Sak Leung","doi":"10.1186/s13073-025-01441-9","DOIUrl":"10.1186/s13073-025-01441-9","url":null,"abstract":"<p><p>Here we present STModule, a Bayesian method developed to identify tissue modules from spatially resolved transcriptomics that reveal spatial components and essential characteristics of tissues. STModule uncovers diverse expression signals in transcriptomic landscapes such as cancer, intraepithelial neoplasia, immune infiltration, outcome-related molecular features and various cell types, which facilitate downstream analysis and provide insights into tumor microenvironments, disease mechanisms, treatment development, and histological organization of tissues. STModule captures a broader spectrum of biological signals compared to other methods and detects novel spatial components. The tissue modules characterized by gene sets demonstrate greater robustness and transferability across different biopsies. STModule: https://github.com/rwang-z/STModule.git .</p>","PeriodicalId":12645,"journal":{"name":"Genome Medicine","volume":"17 1","pages":"18"},"PeriodicalIF":10.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11874447/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143541180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-coding cis-regulatory variants in HK1 cause congenital hyperinsulinism with variable disease severity.","authors":"Jasmin J Bennett, Cécile Saint-Martin, Bianca Neumann, Jonna M E Männistö, Jayne A L Houghton, Susann Empting, Matthew B Johnson, Thomas W Laver, Jonathan M Locke, Benjamin Spurrier, Matthew N Wakeling, Indraneel Banerjee, Antonia Dastamani, Hüseyin Demirbilek, John Mitchell, Markus Stange, Klaus Mohnike, Jean-Baptiste Arnoux, Nick D L Owens, Martin Zenker, Christine Bellanné-Chantelot, Sarah E Flanagan","doi":"10.1186/s13073-025-01440-w","DOIUrl":"10.1186/s13073-025-01440-w","url":null,"abstract":"<p><strong>Background: </strong>We recently reported non-coding variants in a cis-regulatory element of the beta-cell disallowed gene hexokinase 1 (HK1) as a novel cause of congenital hyperinsulinism. These variants lead to a loss of repression of HK1 in pancreatic beta-cells, causing insulin secretion during hypoglycaemia. In this study, we aimed to determine the prevalence, genetics, and phenotype of HK1-hyperinsulinism by screening a large international cohort of patients living with the condition.</p><p><strong>Methods: </strong>We screened the HK1 cis-regulatory region in 1761 probands with hyperinsulinism of unknown aetiology who had been referred to one of three large European genomics laboratories.</p><p><strong>Results: </strong>We identified a HK1 variant in 89/1761 probands (5%) and 63 family members. Within the Exeter HI cohort, these variants accounted for 2.8% of all positive genetic diagnoses (n = 54/1913) establishing this as an important cause of HI. Individuals with a disease-causing variant were diagnosed with hyperinsulinism between birth and 26 years (median: 7 days) with variable response to treatment; 80% were medically managed and 20% underwent pancreatic surgery due to poor response to medical therapy. Glycaemic outcomes varied from spontaneous remission to hypoglycaemia persisting into adulthood. Eight probands had inherited the variant from a parent not reported to have hyperinsulinism (median current age: 39 years), confirming variable penetrance. Two of the 23 novel HK1 variants allowed us to extend the minimal cis-regulatory region from 42 to 46 bp.</p><p><strong>Conclusions: </strong>Non-coding variants within the HK1 cis-regulatory region cause hyperinsulinism of variable severity ranging from neonatal-onset, treatment-resistant disease to being asymptomatic into adulthood. Discovering variants in 89 families confirms HK1 as a major cause of hyperinsulinism and highlights the important role of the non-coding genome in human monogenic disease.</p>","PeriodicalId":12645,"journal":{"name":"Genome Medicine","volume":"17 1","pages":"17"},"PeriodicalIF":10.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11874398/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143541178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LETSmix: a spatially informed and learning-based domain adaptation method for cell-type deconvolution in spatial transcriptomics.","authors":"Yangen Zhan, Yongbing Zhang, Zheqi Hu, Yifeng Wang, Zirui Zhu, Sijing Du, Xiangming Yan, Xiu Li","doi":"10.1186/s13073-025-01442-8","DOIUrl":"10.1186/s13073-025-01442-8","url":null,"abstract":"<p><p>Spatial transcriptomics (ST) enables the study of gene expression in spatial context, but many ST technologies face challenges due to limited resolution, leading to cell mixtures at each spot. We present LETSmix to deconvolve cell types by integrating spatial correlations through a tailored LETS filter, which leverages layer annotations, expression similarities, image texture features, and spatial coordinates to refine ST data. Additionally, LETSmix employs a mixup-augmented domain adaptation strategy to address discrepancies between ST and reference single-cell RNA sequencing data. Comprehensive evaluations across diverse ST platforms and tissue types demonstrate its high accuracy in estimating cell-type proportions and spatial patterns, surpassing existing methods (URL: https://github.com/ZhanYangen/LETSmix ).</p>","PeriodicalId":12645,"journal":{"name":"Genome Medicine","volume":"17 1","pages":"16"},"PeriodicalIF":10.4,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11869467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic alterations and transcriptional phenotypes in circulating free DNA and matched metastatic tumor.","authors":"Nobuyuki Takahashi, Lorinc Pongor, Shivam P Agrawal, Mariya Shtumpf, Ankita Gurjar, Vinodh N Rajapakse, Ahmad Shafiei, Christopher W Schultz, Sehyun Kim, Diana Roame, Paula Carter, Rasa Vilimas, Samantha Nichols, Parth Desai, William Douglas Figg, Mohammad Bagheri, Vladimir B Teif, Anish Thomas","doi":"10.1186/s13073-025-01438-4","DOIUrl":"10.1186/s13073-025-01438-4","url":null,"abstract":"<p><strong>Background: </strong>Profiling circulating cell-free DNA (cfDNA) has become a fundamental practice in cancer medicine, but the effectiveness of cfDNA at elucidating tumor-derived molecular features has not been systematically compared to standard single-lesion tumor biopsies in prospective cohorts of patients. The use of plasma instead of tissue to guide therapy is particularly attractive for patients with small cell lung cancer (SCLC), due to the aggressive clinical course of this cancer, which makes obtaining tumor biopsies exceedingly challenging.</p><p><strong>Methods: </strong>In this study, we analyzed a prospective cohort of 49 plasma samples obtained before, during, and after treatment from 20 patients with recurrent SCLC. We conducted cfDNA low-pass whole genome sequencing (0.1X coverage), comparing it with time-point matched tumor characterized using whole-exome (130X) and transcriptome sequencing.</p><p><strong>Results: </strong>A direct comparison of cfDNA and tumor biopsy revealed that cfDNA not only mirrors the mutation and copy number landscape of the corresponding tumor but also identifies clinically relevant resistance mechanisms and cancer driver alterations not detected in matched tumor biopsies. Longitudinal cfDNA analysis reliably tracks tumor response, progression, and clonal evolution. Sequencing coverage of plasma DNA fragments around transcription start sites showed distinct treatment-related changes and captured the expression of key transcription factors such as NEUROD1 and REST in the corresponding SCLC tumors. This allowed for the prediction of SCLC neuroendocrine phenotypes and treatment responses.</p><p><strong>Conclusions: </strong>cfDNA captures a comprehensive view of tumor heterogeneity and evolution. These findings have significant implications for the non-invasive stratification of SCLC, a disease currently treated as a single entity.</p>","PeriodicalId":12645,"journal":{"name":"Genome Medicine","volume":"17 1","pages":"15"},"PeriodicalIF":10.4,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11863907/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143500581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Intricate interplay of CRISPR-Cas systems, anti-CRISPR proteins, and antimicrobial resistance genes in a globally successful multi-drug resistant Klebsiella pneumoniae clone.","authors":"Jianping Jiang, Astrid V Cienfuegos-Gallet, Tengfei Long, Gisele Peirano, Tingyu Chu, Johann D D Pitout, Barry N Kreiswirth, Liang Chen","doi":"10.1186/s13073-025-01436-6","DOIUrl":"10.1186/s13073-025-01436-6","url":null,"abstract":"","PeriodicalId":12645,"journal":{"name":"Genome Medicine","volume":"17 1","pages":"13"},"PeriodicalIF":10.4,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11852811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The landcape of Helicobacter pylori-mediated DNA breaks links bacterial genotoxicity to its oncogenic potential.","authors":"Hadas Sibony-Benyamini, Rose Jbara, Tania Shubash Napso, Layan Abu-Rahmoun, Daniel Vizenblit, Michal Easton-Mor, Shira Perez, Alexander Brandis, Tamar Leshem, Avi Peretz, Yaakov Maman","doi":"10.1186/s13073-025-01439-3","DOIUrl":"10.1186/s13073-025-01439-3","url":null,"abstract":"<p><strong>Background: </strong>Helicobacter pylori (H. pylori) infection is a significant risk factor for gastric cancer (GC) development. A growing body of evidence suggests a causal link between infection with H. pylori and increased DNA breakage in the host cells. While several mechanisms have been proposed for this damage, their relative impact on the overall bacterial genotoxicity is unknown. Moreover, the link between the formation of DNA damage following infection and the emergence of cancerous structural variants (SV) in the genome of infected cells remained unexplored.</p><p><strong>Methods: </strong>We constructed a high-resolution map of genomic H. pylori-induced recurrent break sites using the END-seq method on AGS human gastric cells before and after infection. We next applied END-seq to cycling and arrested cells to identify the role of DNA replication on break formation. Recurrent H. pylori-mediated break sites were further characterized by analyzing published RNA-seq, DRIP-seq, and GRO-seq data at these sites. γH2AX staining and comet assay were used for DNA breakage quantification. Liquid chromatography-mass spectrometry (LC-MS) assay was used to quantify cellular concentrations of dNTPs.</p><p><strong>Results: </strong>Our data indicated that sites of recurrent H. pylori-mediated DNA breaks are ubiquitous across cell types, localized at replication-related fragile sites, and their breakage is dependent on replication. Consistent with that, we found that H. pylori inflicts nucleotide depletion, and that rescuing the cellular nucleotide pool largely reduced H. pylori-induced DNA breaks. Intriguingly, we found that this genotoxic mechanism operates independently of H. pylori cag pathogenicity island (CagPAI) that encodes for the bacterial type 4 secretion system (T4SS), and its virulence factor, CagA, which was previously implicated in increasing DNA damage by downregulating the DNA damage response. Finally, we show that sites of recurrent H. pylori-mediated breaks coincide with chromosomal deletions observed in patients with intestinal-type GC and that this link potentially elucidates the persistent transcriptional alterations observed in cancer driver genes.</p><p><strong>Conclusions: </strong>Our findings indicate that dNTP depletion by H. pylori is a key component of its genotoxicity and suggest a link between H. pylori genotoxicity and its oncogenic potential.</p>","PeriodicalId":12645,"journal":{"name":"Genome Medicine","volume":"17 1","pages":"14"},"PeriodicalIF":10.4,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11853333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Imaging flow cytometry-based cellular screening elucidates pathophysiology in individuals with Variants of Uncertain Significance.","authors":"Irena Josephina Johanna Muffels, Hans R Waterham, Giuseppina D'Alessandro, Guido Zagnoli-Vieira, Michael Sacher, Dirk J Lefeber, Celine Van der Vinne, Chaim M Roifman, Koen L I Gassen, Holger Rehmann, Desiree Y Van Haaften-Visser, Edward S S Nieuwenhuis, Stephen P Jackson, Sabine A Fuchs, Femke Wijk, Peter van Hasselt","doi":"10.1186/s13073-025-01433-9","DOIUrl":"10.1186/s13073-025-01433-9","url":null,"abstract":"<p><strong>Background: </strong>Deciphering variants of uncertain significance (VUS) represents a major diagnostic challenge, partially due to the lack of easy-to-use and versatile cellular readouts that aid the interpretation of pathogenicity and pathophysiology. To address this challenge, we propose a high-throughput screening of cellular functionality through an imaging flow cytometry (IFC)-based platform.</p><p><strong>Methods: </strong>Six assays to evaluate autophagic-, lysosomal-, Golgi- health, mitochondrial function, ER stress, and NF-κβ activity were developed in fibroblasts. Assay sensitivity was verified with compounds (N = 5) and positive control patients (N = 6). Eight healthy controls and 20 individuals with VUS were screened.</p><p><strong>Results: </strong>All molecular compounds and positive controls showed significant changes on their cognate assays, confirming assay sensitivity. Simultaneous screening of positive control patients on all six assays revealed distinct phenotypic profiles. In addition, individuals with VUS(es) in well-known disease genes showed distinct - but similar-phenotypic profiles compared to patients with pathogenic variants in the same gene.. For all individuals with VUSes in Genes of Uncertain Significance (GUS), we found one or more of six assays were significantly altered. Broadening the screening to an untargeted approach led to the identification of two clusters that allowed for the recognition of altered cell cycle dynamics and DNA damage repair defects. Experimental follow-up of the 'DNA damage repair defect cluster' led to the discovery of highly specific defects in top2cc release from double-strand DNA breaks in one of these individuals, harboring a VUS in the RAD54L2 gene.</p><p><strong>Conclusions: </strong>Our high-throughput IFC-based platform simplifies the process of identifying VUS pathogenicity through six assays and allows for the recognition of useful pathophysiological markers that structure follow-up experiments, thereby representing a novel valuable tool for precise functional diagnostics in genomics.</p>","PeriodicalId":12645,"journal":{"name":"Genome Medicine","volume":"17 1","pages":"12"},"PeriodicalIF":10.4,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11806768/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Digital twins as global learning health and disease models for preventive and personalized medicine.","authors":"Xinxiu Li, Joseph Loscalzo, A K M Firoj Mahmud, Dina Mansour Aly, Andrey Rzhetsky, Marinka Zitnik, Mikael Benson","doi":"10.1186/s13073-025-01435-7","DOIUrl":"10.1186/s13073-025-01435-7","url":null,"abstract":"<p><p>Ineffective medication is a major healthcare problem causing significant patient suffering and economic costs. This issue stems from the complex nature of diseases, which involve altered interactions among thousands of genes across multiple cell types and organs. Disease progression can vary between patients and over time, influenced by genetic and environmental factors. To address this challenge, digital twins have emerged as a promising approach, which have led to international initiatives aiming at clinical implementations. Digital twins are virtual representations of health and disease processes that can integrate real-time data and simulations to predict, prevent, and personalize treatments. Early clinical applications of DTs have shown potential in areas like artificial organs, cancer, cardiology, and hospital workflow optimization. However, widespread implementation faces several challenges: (1) characterizing dynamic molecular changes across multiple biological scales; (2) developing computational methods to integrate data into DTs; (3) prioritizing disease mechanisms and therapeutic targets; (4) creating interoperable DT systems that can learn from each other; (5) designing user-friendly interfaces for patients and clinicians; (6) scaling DT technology globally for equitable healthcare access; (7) addressing ethical, regulatory, and financial considerations. Overcoming these hurdles could pave the way for more predictive, preventive, and personalized medicine, potentially transforming healthcare delivery and improving patient outcomes.</p>","PeriodicalId":12645,"journal":{"name":"Genome Medicine","volume":"17 1","pages":"11"},"PeriodicalIF":10.4,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11806862/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}