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Correcting a pathogenic mitochondrial DNA mutation by base editing in mice.
Sci Transl Med
January 2025
Graduate Program in Human Genetics, University of Miami Miller School of Medicine, 1501 NW 10th Avenue (M-860), Miami, FL 33136, USA.
Primary mitochondrial disorders are most often caused by deleterious mutations in the mitochondrial DNA (mtDNA). Here, we used a mitochondrial DddA-derived cytosine base editor (DdCBE) to introduce a compensatory edit in a mouse model that carries the pathological mutation in the mitochondrial transfer RNA (tRNA) alanine (mt-tRNA) gene. Because the original m.
View Article and Find Full Text PDFCovariate-adjusted construction of gene regulatory networks using a combination of generalized linear model and penalized maximum likelihood.
PLoS One
January 2025
Department of Computing and Mathematics, Manchester Metropolitan University, Manchester, United Kingdom.
Many machine learning techniques have been used to construct gene regulatory networks (GRNs) through precision matrix that considers conditional independence among genes, and finally produces sparse version of GRNs. This construction can be improved using the auxiliary information like gene expression profile of the related species or gene markers. To reach out this goal, we apply a generalized linear model (GLM) in first step and later a penalized maximum likelihood to construct the gene regulatory network using Glasso technique for the residuals of a multi-level multivariate GLM among the gene expressions of one species as a multi-levels response variable and the gene expression of related species as a multivariate covariates.
View Article and Find Full Text PDFColorectal cancer (CRC) is the second leading cause of cancer-related mortality globally. While immunotherapeutic approaches are effective in a subset of CRC patients, the majority of CRC cases receive limited benefits from immunotherapy. This study developed an immune subtype classification system based on diverse immune cells and pathways.
View Article and Find Full Text PDFDetecting Multipartite Entanglement Patterns Using Single-Particle Green's Functions.
Phys Rev Lett
December 2024
Brookhaven National Laboratory, Condensed Matter Physics and Materials Science Division, Upton, New York 11973, USA.
We present a protocol for detecting multipartite entanglement in itinerant many-body electronic systems using single-particle Green's functions. To achieve this, we first establish a connection between the quantum Fisher information and single-particle Green's functions by constructing a set of witness operators built out of single electron creation and destruction operators in a doubled system. This set of witness operators is indexed by a momentum k.
View Article and Find Full Text PDFscHNTL: single-cell RNA-seq data clustering augmented by high-order neighbors and triplet loss.
Bioinformatics
January 2025
School of Computing and Artificial Intelligence, Southwest Jiaotong University, Sichuan 611756, China.
Motivation: The rapid development of single-cell RNA sequencing (scRNA-seq) has significantly advanced biomedical research. Clustering analysis, crucial for scRNA-seq data, faces challenges including data sparsity, high dimensionality, and variable gene expressions. Better low-dimensional embeddings for these complex data should maintain intrinsic information while making similar data close and dissimilar data distant.
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