189 papers
RD-Embed is a lightweight, three-stage representation framework that unifies clinical text and coded signals to significantly improve rare-disease retrieval and diagnosis from heterogeneous electronic health records compared to existing models.
This study utilizes large-scale genome-wide association data to reveal a high degree of shared polygenic architecture between chronic pain and depression, identifying 375 shared genetic loci and specific brain-expressed genes that implicate common biological mechanisms underlying their comorbidity.
This study demonstrates that genomic ascertainment of heterozygous *PALB2* pathogenic variants in large population cohorts reveals significantly elevated risks for breast and pancreatic cancers, as well as increased all-cause mortality, with risks further modified by family history but generally lower than estimates derived from familial ascertainment.
This paper presents a highly accurate, non-invasive preimplantation genetic testing (niPGT) method using reengineered whole-genome amplification and Bayesian haplotype analysis on spent embryo culture medium, which achieved 100% concordance with invasive biopsy controls for monogenic disorders and enabled polygenic risk assessment without requiring modifications to standard IVF workflows.
This study identifies biallelic WDR91 variants as the cause of a severe neurodevelopmental disorder characterized by microcephaly and epilepsy, demonstrating that these mutations lead to disease through impaired endosomal maturation and autophagy dysregulation.
This qualitative and survey study identifies critical knowledge gaps and concerns regarding germline genetic testing for prostate cancer, such as family risk and insurance discrimination, and demonstrates the development of a patient-centered information toolkit to address these needs while highlighting the necessity for further testing across diverse contexts.
This study utilizes functionality-informed fine-mapping on over one million individuals to dissect the highly polygenic architecture of coronary artery disease, identifying 36 high-confidence causal variants and three key biological pathways—lipoprotein metabolism, vascular homeostasis, and inflammation—that drive disease risk.
This study identifies heterozygous CCG repeat expansions in the 5' UTR of the TBC1D7 gene as a novel cause of oculopharyngodistal myopathy (OPDM) in European and mixed-ancestry families, revealing a dominant toxic gain-of-function mechanism and reinforcing the importance of noncoding repeat expansions in neuromuscular disease.
This study leverages a large-scale multi-trait genome-wide association study to identify 282 insulin resistance loci, revealing that adipose-specific dysfunction and systemic inflammatory or calcium signaling pathways are central drivers of the condition, thereby uncovering novel therapeutic targets.
The Russian FSHD registry characterizes a large national cohort of 470 patients, revealing a younger demographic profile, a predominance of 3 D4Z4 repeats, and three distinct disease trajectories that offer a framework for improved patient stratification.
This study integrates single-cell multi-omics with genome-wide association data to identify genetically supported, druggable candidate genes and uncover cell-type-specific causal mechanisms in glioblastomagenesis, highlighting key roles for astrocytes, oligodendrocyte precursor cells, and neurons in tumor development.
SafeGene is a novel, bilingual computational platform developed for Saudi Arabia and Gulf states that leverages region-specific population genetics, consanguinity analysis, and Mendelian models to expand predictive genetic screening from two to over 50 conditions, potentially preventing thousands of affected births annually and saving billions in healthcare costs.
By analyzing sex-stratified adiposity genetics in 2 million individuals, this study reveals that female-specific genetic factors drive endometrial cancer risk through distinct hormone-responsive and insulin-leptin signaling pathways, identifying 26 shared loci and demonstrating that only a fraction of the cancer's genetic variance is directly mediated by adiposity.
This study confirms the pathogenicity of a novel TGFBR2 E431K variant in a patient with Loeys-Dietz syndrome by integrating AI-driven structural modelling with cell-based assays to demonstrate that the mutation disrupts protein stability and aberrantly alters TGF-β signalling.
By partnering with 18 patient organizations to utilize the publicly available GeniE tool for analyzing gnomAD data, this study demonstrates how democratizing genetic prevalence estimates for 22 rare conditions empowers patient advocacy and highlights the dynamic nature of these metrics as genomic databases evolve.
This multi-institute prospective study demonstrates that a novel fragmentomic metric called the regional motif diversity score (rMDS), derived from cell-free DNA end motifs, robustly distinguishes immunotherapy responders from non-responders in head and neck cancer and predicts improved disease-free survival, outperforming established biomarkers like PD-L1 expression and tumor fraction.
This study leverages a large-scale, multi-ancestry multivariate genome-wide association study of millions of participants to identify thousands of genetic loci, revealing that while generalized anxiety disorder and posttraumatic stress disorder share broad genetic mechanisms with a latent internalizing factor, major depressive disorder exhibits a significant proportion of disorder-specific genetic signals linked to distinct neurodevelopmental and stress-responsive pathways.
This study describes the development and fit-for-purpose validation of a highly sensitive and reproducible quantitative LC-MS/MS method for measuring heparan sulfate-derived disaccharides in cerebrospinal fluid, establishing a regulatory-grade biomarker assay essential for monitoring disease progression and therapeutic efficacy in mucopolysaccharidosis type IIIA.
This study identifies FRMPD4 as a causal gene for X-linked non-syndromic sensorineural hearing loss, expanding its known phenotypic spectrum beyond intellectual disability and epilepsy through genetic analysis of affected families and functional validation across Drosophila, zebrafish, and mouse models.
This study presents the first large-scale whole-genome and transcriptome analysis of over 500 treatment-naive breast tumors from India, revealing distinct clinically actionable subtypes, novel mutated genes, and unique genomic features that address the critical underrepresentation of South Asian populations in precision oncology.