Expert consensus on clinical genome sequencing interpretation and reporting.

Genome sequencing (GS) refers to a technology that comprehensively and systematically detects the DNA sequences of an individual's nuclear and mitochondrial genomes. It aims to identify genetic variants and investigate their roles in human health and disease progression. As an emerging diagnostic tool, GS offers significant support for clinical diagnosis due to its high throughput, accuracy, and comprehensiveness.

Somatic variants in SLC35A2 leading to defects in N-glycosylation in mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE).

Mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE) is a new histopathological entity identified in the surgically resected brain tissue of patients with drug-resistant epilepsy. Somatic variants in SLC35A2 have been increasingly identified in MOGHE brain resections. SLC35A2 protein transports uridine 5'-diphosphogalactose (UDP-Gal) into the Golgi lumen, playing a crucial role in the process of N-glycosylation.

SUMMER: an integrated nanopore sequencing pipeline for variants detection and clinical annotation on the human genome.

Long-read sequencing has emerged as a transformative technology in recent years, offering significant potential for the molecular diagnosis of unresolved genetic disorders. Despite its promise, the comprehensive detection and clinical annotation of genomic variants remain intricate and technically demanding. We present SUMMER, an integrated and structured workflow specifically designed to process raw Nanopore sequencing reads.

Lama1 upregulation prolongs the lifespan of the dy/dy mouse model of LAMA2-related congenital muscular dystrophy.

LAMA2-related congenital muscular dystrophy (LAMA2-CMD), characterized by laminin-α2 deficiency, is debilitating and ultimately fatal. To date, no effective therapy has been clinically available. Laminin-α1, which shares significant similarities with laminin-α2, has been proven as a viable compensatory modifier.

Adaptive Selection of Cis-regulatory Elements in the Han Chinese.

Cis-regulatory elements have an important role in human adaptation to the living environment. However, the lag in population genomic cohort studies and epigenomic studies, hinders the research in the adaptive analysis of cis-regulatory elements in human populations. In this study, we collected 4,013 unrelated individuals and performed a comprehensive analysis of adaptive selection of genome-wide cis-regulatory elements in the Han Chinese.

Recent positive selection signatures reveal phenotypic evolution in the Han Chinese population.

Characterizing natural selection signatures and relationships with phenotype spectra is important for understanding human evolution and both biological and pathological mechanisms. Here, we identified 24 genetic loci under recent selection by analyzing rare singletons in 3946 high-depth whole-genome sequencing data of Han Chinese. The loci include immune-related gene regions (MHC cluster, IGH cluster, STING1, and PSG), alcohol metabolism-related gene regions (ADH1B, ALDH2, and ALDH3B2), and the olfactory perception gene OR4C16, in which the MHC cluster, ADH1B, and ALDH2 were also identified by TOPMed and WestLake Biobank.

Characterization of genome-wide STR variation in 6487 human genomes.

Short tandem repeats (STRs) are abundant and highly mutagenic in the human genome. Many STR loci have been associated with a range of human genetic disorders. However, most population-scale studies on STR variation in humans have focused on European ancestry cohorts or are limited by sequencing depth.

NPInter v5.0: ncRNA interaction database in a new era.

Noncoding RNAs (ncRNAs) play key regulatory roles in biological processes by interacting with other biomolecules. With the development of high-throughput sequencing and experimental technologies, extensive ncRNA interactions have been accumulated. Therefore, we updated the NPInter database to a fifth version to document these interactions.

Characterizing mobile element insertions in 5675 genomes.

Mobile element insertions (MEIs) are a major class of structural variants (SVs) and have been linked to many human genetic disorders, including hemophilia, neurofibromatosis, and various cancers. However, human MEI resources from large-scale genome sequencing are still lacking compared to those for SNPs and SVs. Here, we report a comprehensive map of 36 699 non-reference MEIs constructed from 5675 genomes, comprising 2998 Chinese samples (∼26.

NyuWa Genome resource: A deep whole-genome sequencing-based variation profile and reference panel for the Chinese population.

The lack of haplotype reference panels and whole-genome sequencing resources specific to the Chinese population has greatly hindered genetic studies in the world's largest population. Here, we present the NyuWa genome resource, based on deep (26.2×) sequencing of 2,999 Chinese individuals, and construct a NyuWa reference panel of 5,804 haplotypes and 19.

SmProt: A Reliable Repository with Comprehensive Annotation of Small Proteins Identified from Ribosome Profiling.

Small proteins specifically refer to proteins consisting of less than 100 amino acids translated from small open reading frames (sORFs), which were usually missed in previous genome annotation. The significance of small proteins has been revealed in current years, along with the discovery of their diverse functions. However, systematic annotation of small proteins is still insufficient.

Dynamic-BM: multispecies Dynamic BodyMap database from temporal RNA-seq data.

Biological processes, especially developmental processes, are often dynamic. Previous BodyMap projects for human and mouse have provided researchers with portals to tissue-specific gene expression, but these efforts have not included dynamic gene expression patterns. Over the past few years, substantial progress in our understanding of the molecular mechanisms of protein-coding and long noncoding RNA (lncRNA) genes in development processes has been achieved through numerous time series RNA sequencing (RNA-seq) studies.

The long noncoding RNA ASNR regulates degradation of Bcl-2 mRNA through its interaction with AUF1.

The identification and characterization of long non-coding RNAs (lncRNAs) in diverse biological processes has recently developed rapidly. The large amounts of non-coding RNAs scale consistent with developmental complexity in eukaryotes, indicating that most of these transcripts may have functions in the regulation of biological processes and disorder in the organisms. In particular, Understanding of the overall biological significance of lncRNAs in cancers still remains limited.

Long Noncoding RNA ADINR Regulates Adipogenesis by Transcriptionally Activating C/EBPα.

C/EBPα is a critical transcriptional regulator of adipogenesis. How C/EBPα transcription is itself regulated is poorly understood, however, and remains a key question that needs to be addressed for a complete understanding of adipogenic development. Here, we identify a lncRNA, ADINR (adipogenic differentiation induced noncoding RNA), transcribed from a position ∼450 bp upstream of the C/EBPα gene, that orchestrates C/EBPα transcription in vivo.

Transcriptome profiling of esophageal squamous cell carcinoma reveals a long noncoding RNA acting as a tumor suppressor.

Esophageal Squamous Cell Carcinoma (ESCC) is among the most common malignant cancers worldwide. In the past, extensive efforts have been made to characterize the involvement of protein-coding genes in ESCC tumorigenesis but few for long noncoding RNAs (lncRNAs). To investigate the transcriptome profile and functional relevance of lncRNAs, we performed an integrative analysis of a customized combined lncRNA-mRNA microarray and RNA-seq data on ESCCs and matched normal tissues.

Functional Characterization of Long Noncoding RNA Lnc_bc060912 in Human Lung Carcinoma Cells.

Long noncoding RNAs (lncRNAs) are pervasively transcribed in the human genome. Recent studies suggest that the involvement of lncRNAs in human diseases could be far more prevalent than previously appreciated. Here we have identified a lncRNA termed Lnc_bc060912 whose expression is increased in human lung and other tumors.

Distinct MicroRNA Subcellular Size and Expression Patterns in Human Cancer Cells.

Introduction. Small noncoding RNAs have important regulatory functions in different cell pathways. It is believed that most of them mainly play role in gene post-transcriptional regulation in the cytoplasm.

A differential sequencing-based analysis of the C. elegans noncoding transcriptome.

Noncoding RNAs are increasingly being recognized as important players in eukaryote biology. However, despite major efforts in mapping the Caenorhabditis elegans transcriptome over the last couple of years, nonpolyadenylated and intermediate-size noncoding RNAs (is-ncRNAs) are still incompletely explored. We have combined an enzymatic approach with full-length RNA-Seq of is-ncRNAs in C.