NPJ Genomic Medicine最新文献

Environmentally responsible human genomic data governance: points for consideration. 对环境负责的人类基因组数据治理：考虑要点。

IF 5.3 2区医学

NPJ Genomic Medicine Pub Date : 2026-09-03 DOI: 10.1038/s41525-026-00614-8

Narcyz Ghinea, Gabrielle Samuel, Wendy Xin, Emma Bonser, Robert Cook-Deegan, Monica Ferrie, Christopher Gyngell, Margaret Otlowski, Alan Petersen, Bridget Pratt, Susie Roczo-Farkas, Ainsley J Newson

引用次数: 0

aiDIVA - hybrid AI for rare disease diagnostics using evidence-based, machine learning and language models. aiDIVA——利用循证、机器学习和语言模型进行罕见疾病诊断的混合人工智能。

IF 5.3 2区医学

NPJ Genomic Medicine Pub Date : 2026-08-29 DOI: 10.1038/s41525-026-00611-x

Dominic Boceck, Lucia Laugwitz, Marc Sturm, Daniela Bezdan, Axel Gschwind, Tobias B Haack, Stephan Ossowski

{"title":"aiDIVA - hybrid AI for rare disease diagnostics using evidence-based, machine learning and language models.","authors":"Dominic Boceck, Lucia Laugwitz, Marc Sturm, Daniela Bezdan, Axel Gschwind, Tobias B Haack, Stephan Ossowski","doi":"10.1038/s41525-026-00611-x","DOIUrl":"10.1038/s41525-026-00611-x","url":null,"abstract":"Genome sequencing enables accurate detection of genetic variants and is transforming rare disease diagnostics. While data generation is scalable, prioritization and clinical interpretation remain challenging, often requiring expert manual classification. AI-driven decision support systems are therefore needed to assist in causal variant identification or to fully automate large-scale re-analysis of unsolved cases. Existing tools often estimate variant impact on protein function, but few integrate genomic, phenotypic, and clinical annotation data for diagnosis. We present aiDIVA, an ensemble-AI combining statistical and machine learning models trained on genomic and phenotypic data to identify causal variants among tens of thousands per patient. aiDIVA applies a random forest model to classify pathogenicity and generates evidence-based scores for dominant and recessive diseases. These predictions are integrated with clinical metadata to prioritize the most likely causal variants. Large language models further refine and explain results. The aiDIVA-meta model consolidates all scores into a ranked list. aiDIVA-meta reported the causal variant among the top-3 candidates in 97.4% of a pre-training collected cohort with prior evidence in ClinVar or HGMD, and in 93.3% of a post-training collected cohort of previously unreported variants.","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":"11 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13526012/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148857559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Rapid resolution of variants of uncertain significance (VUS). A complementary role for zebrafish in the era of multi-million-dollar therapies. 不确定显著性变异（VUS）的快速分辨。在数百万美元的治疗时代，斑马鱼的补充作用。

IF 5.3 2区医学

NPJ Genomic Medicine Pub Date : 2026-08-10 DOI: 10.1038/s41525-026-00608-6

J Giacomotto

引用次数: 0

Building a Precision Health Ecosystem: Singapore's Approach to Innovation through the Clinical Implementation Pilots. 构建精准健康生态系统：新加坡通过临床实施试点的创新方法。

IF 5.3 2区医学

NPJ Genomic Medicine Pub Date : 2026-07-28 DOI: 10.1038/s41525-026-00594-9

Rebecca Caeser, Doreen Low, Irenaeus Chia, David Matchar, Mikael Hartman, Yi Wang, Jingmei Li, Ken Redekop, Tavintharan Subramaniam, Sharon Li Ting Pek, Hwee Lin Wee, Goh Boon Cher, Suchin Virabhak, Shih Wee Seow, John C Chambers, Patrick Tan, Ee Shien Tan, Kar Hui Ng, Joanne Ngeow, E Shyong Tai

引用次数: 0

The clinical utility of carrier screening. 携带者筛查的临床应用。

IF 5.3 2区医学

NPJ Genomic Medicine Pub Date : 2026-07-25 DOI: 10.1038/s41525-026-00601-z

Mia J Gruzin, Leslie Burnett

{"title":"The clinical utility of carrier screening.","authors":"Mia J Gruzin, Leslie Burnett","doi":"10.1038/s41525-026-00601-z","DOIUrl":"10.1038/s41525-026-00601-z","url":null,"abstract":"Carrier screening aims to identify couples at risk of having children with serious genetic disorders. However, screening panels vary markedly in size, gene content and price, with little guidance to assess clinical utility or value. We analysed 89 carrier screening panels from 30 global providers, modelling test performance using pathogenic variants from gnomAD v4.1.0 and ClinVar across ten ancestry groups and two synthetic populations (representing the United States and Australia). We evaluated how panel size, content, price and clinical utility interrelate. We also compared value per dollar spent to guide clinical decision-making and fair pricing. Clinical utility showed no consistent relationship with panel size or price. Instead, mid-sized, pan-ancestry \"Goldilocks\" panels delivered the greatest utility, outperforming both smaller and larger panels, while delivering more equitable outcomes. We developed a visual \"clinical utility meter\" to compare relative test performance and an \"efficiency frontier\" framework to identify the best value tests for a given price. This data-driven framework and visual tool can support rational test design and selection for value-based laboratory medicine.","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":"11 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13434709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148670202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Recall-by-genotype of neurodevelopmental disorder copy number variants in a multi-ancestry, healthcare-system biobank. 多祖先医疗保健系统生物库中神经发育障碍拷贝数变异的基因型回忆。

IF 5.3 2区医学

NPJ Genomic Medicine Pub Date : 2026-07-16 DOI: 10.1038/s41525-026-00597-6

Nina Zaks, Behrang Mahjani, Abraham Reichenberg, Rebecca Birnbaum

{"title":"Recall-by-genotype of neurodevelopmental disorder copy number variants in a multi-ancestry, healthcare-system biobank.","authors":"Nina Zaks, Behrang Mahjani, Abraham Reichenberg, Rebecca Birnbaum","doi":"10.1038/s41525-026-00597-6","DOIUrl":"10.1038/s41525-026-00597-6","url":null,"abstract":"Clinical biobanks linking electronic health records (EHRs) with genotype data enable the study of genomic risk factors in real-world populations. However, recall-by-genotype (RbG) of psychiatric risk variants in diverse healthcare-system biobanks remains scarce. Leveraging BioMe, a multi-ancestry biobank within the Mount Sinai Health System, we recalled carriers of rare copy number variants (CNVs) that confer increased risk for neurodevelopmental disorders (NDDs) to establish empirical benchmarks for RbG implementation. We recontacted 892 participants: 335 NDD CNV carriers, 217 individuals with schizophrenia without NDD CNVs, and 340 neurotypical controls without NDD CNVs. Participants completed clinical and cognitive assessments. Overall, 18% of recontacted participants responded to recruitment, and 8% completed the study: 30 NDD CNV carriers, 20 individuals with schizophrenia, and 23 controls. The mean age was 48.8 years, 66% were female, and self-reported ancestry was 37% African, 34% Hispanic, and 26% European. Seventy percent of NDD CNV carriers had at least one neuropsychiatric or developmental condition, including mood or anxiety disorders (40%). Among 22 NDD CNV carriers at loci implicated in impaired cognition, performance was lower than controls on Digit Span Backward (β = -1.76, FDR = 0.04) and Digit Span Sequencing (β = -2.01, FDR = 0.04). NDD CNV carriers also outperformed the schizophrenia group on verbal learning (β = 4.5, FDR = 0.05). Recall of individuals-including those with psychiatric illness-yielded phenotypes not captured in EHRs and provides empirical benchmarks relevant to RbG implementation and precision psychiatry in diverse healthcare systems.","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148471772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Specimen quality shapes the actionable genomic landscape in comprehensive cancer genomic profiling. 在全面的癌症基因组分析中，标本质量塑造了可操作的基因组景观。

IF 5.3 2区医学

NPJ Genomic Medicine Pub Date : 2026-07-11 DOI: 10.1038/s41525-026-00595-8

Hikaru Nakahara, Hiroaki Niitsu, Masanori Motonaga, Hiroaki Matsuo, Koji Arihiro, C Nelson Hayes, Takao Hinoi

{"title":"Specimen quality shapes the actionable genomic landscape in comprehensive cancer genomic profiling.","authors":"Hikaru Nakahara, Hiroaki Niitsu, Masanori Motonaga, Hiroaki Matsuo, Koji Arihiro, C Nelson Hayes, Takao Hinoi","doi":"10.1038/s41525-026-00595-8","DOIUrl":"https://doi.org/10.1038/s41525-026-00595-8","url":null,"abstract":"Comprehensive genomic profiling (CGP) is widely used to identify actionable alterations and guide precision oncology, yet only a minority of tested patients receive genome-matched therapies, underscoring a gap between genomic findings and clinical benefit. We hypothesized that this gap may partly reflect variation in the reliability and interpretability of genomic information generated from specimens of different quality and by different assay modalities. To examine this possibility, we performed a retrospective multicenter analysis of 2002 CGP tests conducted between 2019 and 2025 across 13 institutions in Japan. Detection of short variants, copy number alterations (CNAs), structural variants, and genomic signatures, including microsatellite instability, tumor mutational burden, and homologous recombination deficiency signature, was compared among FoundationOne CDx specimens classified as pass (F1-pass) or qualified (F1-qual) and liquid-based CGP (liq-CGP). Short variant detection remained largely preserved in F1-qual specimens, whereas CNA and genomic signature detection were substantially reduced. In pancreatic adenocarcinoma, KRAS variants were detected in 93% of F1-pass, 88% of F1-qual, and 57% of liq-CGP cases. These differences affected the proportion of patients offered genome-matched therapies. Machine learning models predicted QC status with area-under-the-curve values of 0.72-0.78. Our findings support QC-aware CGP selection in routine precision oncology.","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148422917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Evolutionary history of LRRK2 and PRKN in leprosy and Parkinson's disease. LRRK2和PRKN在麻风病和帕金森病中的进化历史

IF 5.3 2区医学

NPJ Genomic Medicine Pub Date : 2026-07-11 DOI: 10.1038/s41525-026-00596-7

Rachele Cagliani, Uberto Pozzoli, Diego Forni, Alessandra Mozzi, Manuela Sironi

{"title":"Evolutionary history of LRRK2 and PRKN in leprosy and Parkinson's disease.","authors":"Rachele Cagliani, Uberto Pozzoli, Diego Forni, Alessandra Mozzi, Manuela Sironi","doi":"10.1038/s41525-026-00596-7","DOIUrl":"https://doi.org/10.1038/s41525-026-00596-7","url":null,"abstract":"LRRK2 (leucine-rich repeat kinase 2) and Parkin (PRKN) act in shared pathways and are implicated in Parkinson's disease (PD), leprosy, and other diseases. While leprosy likely imposed strong evolutionary pressure, PD's relatively late onset renders it largely invisible to natural selection. We examined the evolutionary history of LRRK2 and PRKN in primates and human populations and found evidence of positive selection on both genes, alongside strong constraint at LRRK2 disease-associated sites. Gibbons were found to carry a pathogenic PRKN mutation (R33Q) causing protein instability. Using ancient DNA, we traced the dynamics of LRRK2 and PRKN variants in Europe and showed that the common PD risk allele LRRK2 G2019S-also protective against salmonellosis-was absent in Paleolithic populations but rose rapidly during the Early Neolithic, likely driven by selection from emerging human-adapted Salmonella. Four leprosy susceptibility variants in PRKN and other loci increased in frequency before the Middle Ages, with little evidence of strong selection during the medieval epidemic itself. Together, these results link a major PD mutation to ancient infectious pressures and suggest that pathogen-driven selection shaped leprosy susceptibility in Europe prior to its medieval peak.","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148422935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Family experiences of receiving treatment recommendations in a precision medicine trial for poor-prognosis childhood cancer. 在一项预后不良的儿童癌症的精准医学试验中接受治疗建议的家庭经验。

IF 5.3 2区医学

NPJ Genomic Medicine Pub Date : 2026-07-03 DOI: 10.1038/s41525-026-00591-y

Kate Hetherington, Jacqueline D Hunter, Mark W Donoghoe, Maeve McGillycuddy, Brittany C McGill, Eden G Robertson, Vanessa Tyrrell, Loretta M S Lau, Jonathon M Marron, Katherine M Tucker, Glenn M Marshall, Janine Vetsch, Michelle Haber, David Malkin, Marion K Mateos, Tracey A O'Brien, David S Ziegler, Claire E Wakefield

{"title":"Family experiences of receiving treatment recommendations in a precision medicine trial for poor-prognosis childhood cancer.","authors":"Kate Hetherington, Jacqueline D Hunter, Mark W Donoghoe, Maeve McGillycuddy, Brittany C McGill, Eden G Robertson, Vanessa Tyrrell, Loretta M S Lau, Jonathon M Marron, Katherine M Tucker, Glenn M Marshall, Janine Vetsch, Michelle Haber, David Malkin, Marion K Mateos, Tracey A O'Brien, David S Ziegler, Claire E Wakefield","doi":"10.1038/s41525-026-00591-y","DOIUrl":"https://doi.org/10.1038/s41525-026-00591-y","url":null,"abstract":"Precision medicine trials may generate new treatment options for children with poor-prognosis cancer. We examined families' experiences of receiving treatment recommendations in the Australian PRISM trial (Australian and New Zealand Clinical Trials Registry: NCT03336931; https://clinicaltrials.gov/study/NCT03336931; registration date 08/11/2017). Parents and patients (12-17 years) completed questionnaires at enrolment (T0; n = 303 and n = 31) and following results and any treatment recommendations (T1; n = 144 and n = 8). Fifty-eight parents completed an interview (T1). At T0, most parents and patients expected to benefit from participation (87%) and receive a treatment recommendation (68%). Of the 70% of parents who received a treatment recommendation, half recalled this information. Parents felt that treatment recommendations offered hope and options; their absence brought disappointment, but also reassurance that all options were explored. Parents reported high involvement (93/100) and satisfaction (95/100) in treatment decisions. Receiving a treatment recommendation was not associated with regret about trial participation (p > 0.05). Our findings underscore precision medicine's value for families in the setting of a poor-prognosis child with cancer.","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148382603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

An EHR-based framework for modeling growth curves and constructing growth centile charts for genetic disorders. 一个基于ehr的框架，用于建模生长曲线和构建遗传疾病的生长百分位图。

IF 5.3 2区医学

NPJ Genomic Medicine Pub Date : 2026-07-03 DOI: 10.1038/s41525-026-00592-x

Cathy Shyr, Rory J Tinker, Rebekah F Brown, Adam Wright, Josh F Peterson, John A Phillips, S Trent Rosenbloom, Lisa Bastarache

{"title":"An EHR-based framework for modeling growth curves and constructing growth centile charts for genetic disorders.","authors":"Cathy Shyr, Rory J Tinker, Rebekah F Brown, Adam Wright, Josh F Peterson, John A Phillips, S Trent Rosenbloom, Lisa Bastarache","doi":"10.1038/s41525-026-00592-x","DOIUrl":"10.1038/s41525-026-00592-x","url":null,"abstract":"Growth modeling is central to human genetics, as deviations from typical growth can signal an underlying disorder. In this cohort study, we developed a generalizable framework for generating growth charts across genetic conditions using electronic health records (EHR). Leveraging 22 years of longitudinal EHR data from 452,470 patients across 15 genetic conditions and unaffected individuals, we generated sex- and condition-specific growth charts using Generalized Additive Models for Location, Scale, and Shape, and quantified differences in size, timing, and intensity using SuperImposition by Translation and Rotation (SITAR). SITAR-derived growth parameters showed strong concordance with established annotations in OMIM and Orphanet, and identified previously unreported growth patterns. We stratified cystic fibrosis by CFTR functional class and observed greater growth impairment in individuals with homozygous minimal-function variants compared to those with residual function. This framework provides a generalizable approach for leveraging EHR data to refine genotype-phenotype relationships and enable continuous updating of growth charts across genetic conditions.","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13338247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148382669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0