Non-canonical antigens are the largest fraction of peptides presented by MHC class I in mismatch repair deficient murine colorectal cancer
ConclusionsOur results suggest that —in comparison to MMR proficient CRC—MMRd tumors generate a significantly higher number of non-canonical mutated peptides able to elicit T cell responses. These results reveal the importance of evaluating the diversity of neoepitope repertoire in MMRd tumors. (Source: Genome Medicine)
Source: Genome Medicine - January 19, 2024 Category: Genetics & Stem Cells Source Type: research
Spatial multi-omics: novel tools to study the complexity of cardiovascular diseases
AbstractSpatial multi-omic studies have emerged as a promising approach to comprehensively analyze cells in tissues, enabling the joint analysis of multiple data modalities like transcriptome, epigenome, proteome, and metabolome in parallel or even the same tissue section. This review focuses on the recent advancements in spatial multi-omics technologies, including novel data modalities and computational approaches. We discuss the advancements in low-resolution and high-resolution spatial multi-omics methods which can resolve up to 10,000 of individual molecules at subcellular level. By applying and integrating these techn...
Source: Genome Medicine - January 18, 2024 Category: Genetics & Stem Cells Source Type: research
The impact of damaging epilepsy and cardiac genetic variant burden in sudden death in the young
ConclusionsWhile damaging cardiomyopathy and arrhythmia genes are recognized contributors to SDY, we also observed an enrichment in epilepsy-related genes in the SDY cohort and a correlation between rare epilepsy variation and younger age at death. These findings emphasize the importance of considering epilepsy genes when evaluating SDY. (Source: Genome Medicine)
Source: Genome Medicine - January 16, 2024 Category: Genetics & Stem Cells Source Type: research
Multimodal epigenetic sequencing analysis (MESA) of cell-free DNA for non-invasive colorectal cancer detection
ConclusionsTogether, MESA stands as a major advancement in the field by utilizing comprehensive and complementary epigenetic profiles of cfDNA for effective non-invasive cancer detection. (Source: Genome Medicine)
Source: Genome Medicine - January 16, 2024 Category: Genetics & Stem Cells Source Type: research
Genomic and transcriptomic analysis of breast cancer identifies novel signatures associated with response to neoadjuvant chemotherapy
ConclusionsOur study has revealed genomic and transcriptomic landscape changes following NAC in BC, and identified novel biomarkers (CDKAL1P409L,ADGRA2 andADRB3) underlying chemotherapy resistance and poor prognosis, which could guide the development of personalized treatments for BC. (Source: Genome Medicine)
Source: Genome Medicine - January 12, 2024 Category: Genetics & Stem Cells Source Type: research
Unsupervised spatially embedded deep representation of spatial transcriptomics
We present SEDR, which uses a deep autoencoder coupled with a masked self-supervised learning mechanism to construct a low-dimensional latent representation of gene expression, which is then simultaneously embedded with the corresponding spatial information through a variational graph autoencoder. SEDR achieved higher clustering performance on manually annotated 10 × Visium datasets and better scalability on high-resolution spatial transcriptomics datasets than existing methods. Additionally, we show SEDR’s ability to impute and denoise gene expression (URL:https://github.com/JinmiaoChenLab/SEDR/). (Source: Genome Medicine)
Source: Genome Medicine - January 12, 2024 Category: Genetics & Stem Cells Source Type: research
Defining type 2 diabetes polygenic risk scores through colocalization and network-based clustering of metabolic trait genetic associations
ConclusionsWe successfully partitioned T2D genetic variants into phenotypic pathways using a colocalization first approach. Partitioned PRSs were associated to unique metabolic and clinical outcomes indicating successful partitioning of disease heterogeneity. Our work expands on previous approaches by providing stronger inferences of shared causal variants, causality, and directionality of GWAS variant-trait associations. (Source: Genome Medicine)
Source: Genome Medicine - January 10, 2024 Category: Genetics & Stem Cells Source Type: research
Transcriptional signals of transformation in human cancer
ConclusionsOur findings provide a nuanced picture of transformation in human cancer, indicating cancer-specific rather than universal patterns of transformation pervade adult epithelial cancers. (Source: Genome Medicine)
Source: Genome Medicine - January 9, 2024 Category: Genetics & Stem Cells Source Type: research
Rare copy-number variants as modulators of common disease susceptibility
ConclusionsOur results shed light on the prominent role of rare CNVs in determining common disease susceptibility within the general population and provide actionable insights for anticipating later-onset comorbidities in carriers of recurrent CNVs. (Source: Genome Medicine)
Source: Genome Medicine - January 8, 2024 Category: Genetics & Stem Cells Source Type: research
MAGPIE: accurate pathogenic prediction for multiple variant types using machine learning approach
We present a method named Multimodal Annotation Generated Pathogenic Impact Evaluator (MAGPIE) that predicts the pathogenicity of multi-type variants. MAGPIE uses the ClinVar dataset for training and demonstrates superior performance in both the independent test set and multiple orthogonal validation datasets, accurately predicting variant pathogenicity. Notably, MAGPIE performs best in predicting the pathogenicity of rare variants and highly imbalanced datasets. Overall, results underline the robustness of MAGPIE as a valuable tool for predicting pathogenicity in various types of human genome variations. MAGPIE is availab...
Source: Genome Medicine - January 8, 2024 Category: Genetics & Stem Cells Source Type: research
Correction: Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19
(Source: Genome Medicine)
Source: Genome Medicine - January 6, 2024 Category: Genetics & Stem Cells Source Type: research
Combining a prioritization strategy and functional studies nominates 5 ’UTR variants underlying inherited retinal disease
ConclusionsThis study demonstrates the importance of 5 ’UTR variants implicated in IRDs and provides a systematic approach for 5’UTR annotation and validation that is applicable to other inherited diseases. (Source: Genome Medicine)
Source: Genome Medicine - January 6, 2024 Category: Genetics & Stem Cells Source Type: research
Using multi-scale genomics to associate poorly annotated genes with rare diseases
ConclusionsWe highlight clade-based phylogenetic profiling as a powerful systematic approach for prioritizing potential disease genes. Our study showcases the efficacy of EvORanker in associating poorly annotated genes to disease phenotypes observed in patients. The EvORanker server is freely available athttps://ccanavati.shinyapps.io/EvORanker/. (Source: Genome Medicine)
Source: Genome Medicine - January 4, 2024 Category: Genetics & Stem Cells Source Type: research
Single-cell transcriptomic analysis reveals tumor cell heterogeneity and immune microenvironment features of pituitary neuroendocrine tumors
ConclusionsOur data and analysis manifested the basic cell types in the normal pituitary and inherent heterogeneity of PitNETs, identified several features of the tumor immune microenvironments, and found a novel epithelial cell sub-population with aggressive signatures across all the studied cases. (Source: Genome Medicine)
Source: Genome Medicine - January 2, 2024 Category: Genetics & Stem Cells Source Type: research
Systematic analysis of Mendelian disease-associated gene variants reveals new classes of cancer-predisposing genes
ConclusionsOur findings suggest a possible cancer progression mechanism through metabolic profile alterations. Overall, our data indicates that pathogenic OMIM gene variants contribute to cancer progression and introduces new CPG classifications potentially underpinning diverse tumorigenesis mechanisms. (Source: Genome Medicine)
Source: Genome Medicine - December 25, 2023 Category: Genetics & Stem Cells Source Type: research
