Glycosylation is the most abundant and diverse form of post-translational modification of proteins that is common to all eukaryotic cells. Enzymatic glycosylation of proteins involves a complex ...metabolic network and different types of glycosylation pathways that orchestrate enormous amplification of the proteome in producing diversity of proteoforms and its biological functions. The tremendous structural diversity of glycans attached to proteins poses analytical challenges that limit exploration of specific functions of glycosylation. Major advances in quantitative transcriptomics, proteomics and nuclease-based gene editing are now opening new global ways to explore protein glycosylation through analysing and targeting enzymes involved in glycosylation processes. In silico models predicting cellular glycosylation capacities and glycosylation outcomes are emerging, and refined maps of the glycosylation pathways facilitate genetic approaches to address functions of the vast glycoproteome. These approaches apply commonly available cell biology tools, and we predict that use of (single-cell) transcriptomics, genetic screens, genetic engineering of cellular glycosylation capacities and custom design of glycoprotein therapeutics are advancements that will ignite wider integration of glycosylation in general cell biology.
Cross-species comparative analyses of single-cell RNA sequencing (scRNA-seq) data allow us to explore, at single-cell resolution, the origins of the cellular diversity and evolutionary mechanisms ...that shape cellular form and function. Cell-type assignment is a crucial step to achieve that. However, the poorly annotated genome and limited known biomarkers hinder us from assigning cell identities for nonmodel species. Here, we design a heterogeneous graph neural network model, CAME, to learn aligned and interpretable cell and gene embeddings for cross-species cell-type assignment and gene module extraction from scRNA-seq data. CAME achieves significant improvements in cell-type characterization across distant species owing to the utilization of non-one-to-one homologous gene mapping ignored by early methods. Our large-scale benchmarking study shows that CAME significantly outperforms five classical methods in terms of cell-type assignment and model robustness to insufficiency and inconsistency of sequencing depths. CAME can transfer the major cell types and interneuron subtypes of human brains to mouse and discover shared cell-type-specific functions in homologous gene modules. CAME can align the trajectories of human and macaque spermatogenesis and reveal their conservative expression dynamics. In short, CAME can make accurate cross-species cell-type assignments even for nonmodel species and uncover shared and divergent characteristics between two species from scRNA-seq data.
In contrast to artificial intelligence and machine learning approaches, KEGG (https://www.kegg.jp) has relied on human intelligence to develop “models” of biological systems, especially in the form ...of KEGG pathway maps that are manually created by capturing knowledge from published literature. The KEGG models can then be used in biological big data analysis, for example, for uncovering systemic functions of an organism hidden in its genome sequence through the simple procedure of KEGG mapping. Here we present an updated version of KEGG Mapper, a suite of KEGG mapping tools reported previously (Kanehisa and Sato, Protein Sci 2020; 29:28–35), together with the new versions of the KEGG pathway map viewer and the BRITE hierarchy viewer. Significant enhancements have been made for BRITE mapping, where the mapping result can be examined by manipulation of hierarchical trees, such as pruning and zooming. The tree manipulation feature has also been implemented in the taxonomy mapping tool for linking KO (KEGG Orthology) groups and modules to phenotypes.
Much has been learned since the early 1960s about histone post-translational modifications (PTMs) and how they affect DNA-templated processes at the molecular level. This understanding has been ...bolstered in the past decade by the identification of new types of histone PTM, the advent of new genome-wide mapping approaches and methods to deposit or remove PTMs in a locally and temporally controlled manner. Now, with the availability of vast amounts of data across various biological systems, the functional role of PTMs in important processes (such as transcription, recombination, replication, DNA repair and the modulation of genomic architecture) is slowly emerging. This Review explores the contribution of histone PTMs to the regulation of genome function by discussing when these modifications play a causative (or instructive) role in DNA-templated processes and when they are deposited as a consequence of such processes, to reinforce and record the event. Important advances in the field showing that histone PTMs can exert both direct and indirect effects on genome function are also presented.
Spatiotemporal gene expression programmes are orchestrated by transcriptional enhancers, which are key regulatory DNA elements that engage in physical contacts with their target-gene promoters, often ...bridging considerable genomic distances. Recent progress in genomics, genome editing and microscopy methodologies have enabled the genome-wide mapping of enhancer-promoter contacts and their functional dissection. In this Review, we discuss novel concepts on how enhancer-promoter interactions are established and maintained, how the 3D architecture of mammalian genomes both facilitates and constrains enhancer-promoter contacts, and the role they play in gene expression control during normal development and disease.
While nuclear compartmentalization is an essential feature of three-dimensional genome organization, no genomic method exists for measuring chromosome distances to defined nuclear structures. In this ...study, we describe TSA-Seq, a new mapping method capable of providing a "cytological ruler" for estimating mean chromosomal distances from nuclear speckles genome-wide and for predicting several Mbp chromosome trajectories between nuclear compartments without sophisticated computational modeling. Ensemble-averaged results in K562 cells reveal a clear nuclear lamina to speckle axis correlated with a striking spatial gradient in genome activity. This gradient represents a convolution of multiple spatially separated nuclear domains including two types of transcription "hot zones." Transcription hot zones protruding furthest into the nuclear interior and positioning deterministically very close to nuclear speckles have higher numbers of total genes, the most highly expressed genes, housekeeping genes, genes with low transcriptional pausing, and super-enhancers. Our results demonstrate the capability of TSA-Seq for genome-wide mapping of nuclear structure and suggest a new model for spatial organization of transcription and gene expression.
Reading, writing and erasing mRNA methylation Zaccara, Sara; Ries, Ryan J; Jaffrey, Samie R
Nature reviews. Molecular cell biology,
10/2019, Letnik:
20, Številka:
10
Journal Article
Recenzirano
RNA methylation to form N
-methyladenosine (m
A) in mRNA accounts for the most abundant mRNA internal modification and has emerged as a widespread regulatory mechanism that controls gene expression ...in diverse physiological processes. Transcriptome-wide m
A mapping has revealed the distribution and pattern of m
A in cellular RNAs, referred to as the epitranscriptome. These maps have revealed the specific mRNAs that are regulated by m
A, providing mechanistic links connecting m
A to cellular differentiation, cancer progression and other processes. The effects of m
A on mRNA are mediated by an expanding list of m
A readers and m
A writer-complex components, as well as potential erasers that currently have unclear relevance to m
A prevalence in the transcriptome. Here we review new and emerging methods to characterize and quantify the epitranscriptome, and we discuss new concepts - in some cases, controversies - regarding our understanding of the mechanisms and functions of m
A readers, writers and erasers.
Diverse microbial communities of bacteria, archaea, viruses and single-celled eukaryotes have crucial roles in the environment and in human health. However, microbes are frequently difficult to ...culture in the laboratory, which can confound cataloging of members and understanding of how communities function. High-throughput sequencing technologies and a suite of computational pipelines have been combined into shotgun metagenomics methods that have transformed microbiology. Still, computational approaches to overcome the challenges that affect both assembly-based and mapping-based metagenomic profiling, particularly of high-complexity samples or environments containing organisms with limited similarity to sequenced genomes, are needed. Understanding the functions and characterizing specific strains of these communities offers biotechnological promise in therapeutic discovery and innovative ways to synthesize products using microbial factories and can pinpoint the contributions of microorganisms to planetary, animal and human health.
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