?PISCIS: Spot Detection in FISH Images??, ??CHOPOFF for CRISPR Off-Target Detection???, ??RASAM: Hyperaccessible Regions in DNA??
Bioinformer Weekly Roundup
Stay Updated with the Latest in Bioinformatics!
Issue: 70 | Date: 24 January 2025
?? Welcome to the Bioinformer Weekly Roundup!
In this newsletter, we curate and bring you the most captivating stories, developments, and breakthroughs from the world of bioinformatics. Whether you are a seasoned researcher, a student, or simply curious about the intersection of biology and data science, we have got you covered. Subscribe now to stay ahead in the exciting realm of Bioinformatics!
?? Featured Research
This study benchmarks five cell type annotation methods (SingleR, Azimuth, RCTD,?scPred,?scmapCell) for spatial transcriptomics using 10x Xenium data of human breast cancer, emphasizing the need for a well-annotated reference dataset.?SingleR?was reported as the best-performing tool, being fast, accurate, and easy to use, closely matching manual results.?
This study shows that inhibiting mitochondrial respiratory complex I (CI) by deleting Ndufs4 or Ndufs6 enhances tumour immunogenicity and sensitivity to immune checkpoint blockade (ICB) in melanoma and breast cancer models. Deleting Ndufs4 increases MHC class I co-activator Nlrc5 and antigen presentation components, driven by mitochondrial acetyl-CoA and histone H3K27 acetylation. This selective CI inhibition restricts tumour growth and boosts T cell surveillance and ICB responsiveness.?
This study looks at gene expression in?prospermatogonia, spermatogonia, and testicular somatic cells at four stages using?scRNA-seq. It finds five molecular states in?prospermatogonia?and shows that Leydig and peritubular myoid cells help transmit signals. The study highlights the role of?bHLH?transcription factors in?prospermatogonial?development and shows that overexpressing Id2 disrupts their transition to spermatogonia. These findings provide insights into how spermatogonia develop.?
Gut bacterium Intestinimonas butyriciproducens improves host metabolic health: evidence from cohort and animal intervention studies | Microbiome?
This study explores the role of?Intestinimonas?butyriciproducens?in metabolic disorders through faecal metagenomic analysis. Researchers found that this bacterium and its?fructoselysine?fermentation genes are linked to lower BMI, triglycerides, HbA1c, and fasting insulin levels. In obesity mouse models, supplementation with I.?butyriciproducens?reduced weight gain, hyperglycemia, and adiposity, while enhancing anti-inflammatory pathways and insulin signalling. These findings suggest that I.?butyriciproducens?could be a promising therapy for metabolic diseases.?
This study tackles the challenge of using traditional reference genes like GAPDH or PGK1 for accurate RT-qPCR analysis in hypoxic breast tumours. By analysing RNA-seq data, researchers identified and validated RPLP1 and RPL27 as optimal reference genes for Luminal A and TNBC cells under both?normoxic?and hypoxic conditions, enhancing the precision of gene expression studies in hypoxic breast cancer research.?
This study characterizes pituitary-resident macrophages (pitM?s) using single-cell transcriptomics, fate mapping, and imaging, revealing their heterogeneity and spatial specialization. It shows that?pitM?s?originate from yolk sac progenitors and self-renew independently of bone marrow-derived monocytes. The research highlights the role of macrophages in regulating hormonal balance in the pituitary gland through extracellular ATP signalling, enhancing our understanding of immune-endocrine interactions.?
This study presents a comprehensive atlas of the mouse upper respiratory epithelium using single-cell RNA sequencing and spatial validation. It identifies 17 cell types organized into three compartments:?pharyngolaryngeal, tracheobronchial, and submucosal gland epithelium. The findings highlight distinct transcriptional programs and spatial distributions, enhancing our understanding of immune defence, injury repair, and cellular behaviour in homeostasis and disease.?
This study reveals that conventional dendritic cells (cDCs) mature by using internal cholesterol to form lipid nanodomains, enhancing maturation markers and immune signalling. This process relies on cholesterol transport via NPC1 and is regulated by the receptor tyrosine kinase AXL. Deleting AXL improves?cDC?maturation and anti-tumour immunity, highlighting cholesterol mobilization and AXL as key factors in?cDC?maturation and potential therapeutic targets.?
??? Latest Tools
EPSD 2.0: An Updated Database of Protein Phosphorylation Sites across Eukaryotic Species | bioRxiv??
EPSD 2.0 is an updated database of protein phosphorylation sites across eukaryotic species. It includes 2,769,163 experimentally identified phosphorylation sites in 362,707 phosphoproteins from 223 eukaryotes. The database integrates new high-throughput?phosphoproteomic?data and annotations from multiple public databases, providing a comprehensive resource for studying phosphorylation.
The EPSD 2.0 database is accessible online?here.?
VirDetector?is a bioinformatic pipeline designed for virus surveillance using nanopore sequencing. It automates the installation of required programs and databases, allowing users to execute all steps with a single command. The pipeline preprocesses samples, performs taxonomic classification, reconstructs viral genomes, and conducts phylogenetic analyses. This streamlined workflow is user-friendly and efficient for monitoring viral pathogens.
The source code is available?here.
Piscis is a deep learning algorithm designed for accurate spot detection in fluorescence microscopy images. It utilizes a novel loss function, SmoothF1, which approximates the F1 score to penalize false positives and negatives, enhancing the accuracy of RNA FISH image analysis. Piscis was trained on a diverse dataset, outperforming other spot detection methods and enabling high-throughput analysis without manual parameter tuning.
Piscis code library can be found at the GitHub repository here.?
getphylo?is a Python tool for the rapid generation of multi-locus phylogenetic trees from annotated genomes. It identifies orthologues heuristically and infers phylogenies using a concatenated alignment of coding sequences by maximum likelihood.?getphylo?is benchmarked against existing tools, demonstrating comparable quality in a fraction of the time, and is flexible across various datasets, including bacterial and eukaryotic genomes.
The source code is available here.?
CHOPOFF is a tool designed for fast and sensitive CRISPR off-target detection using symbolic alignments. It efficiently identifies off-targets without sacrificing sensitivity and introduces data structures for near-instant alignment-free probabilistic ranking of guides based on their off-target counts. This tool supports mismatches, bulges, and genomic sequence variations, outperforming state-of-the-art methods in both speed and accuracy.
The code and datasets are available?here.?
The article introduces BiomiX, a bioinformatics tool designed to simplify the analysis and integration of multiomics data. It combines various omics data using packages like DESeq2/Limma and performs analyses such as metabolomics annotation and methylomics analysis. The tool also incorporates Multi-Omics Factor Analysis (MOFA) for identifying shared sources of variation and provides interactive data visualization for personalized analysis. BiomiX aims to make multiomics analysis accessible to non-experts by offering a wide range of parameters and user-friendly features.
The link to access BiomiX is here.
The article introduces GLiDe, a web-based tool for designing sgRNA libraries for CRISPRi screening in prokaryotes. It incorporates a quality control framework to minimize off-target effects and includes a database of 1,397 common prokaryotic species. GLiDe also allows designing sgRNAs for newly discovered organisms by accepting uploaded design resources. The tool aims to provide a user-friendly pipeline for genome-scale CRISPRi sgRNA library construction.
领英推荐
The article introduces DFAST_QC, a tool for quality assessment and taxonomic identification of prokaryotic genomes. It combines genome-distance calculations using MASH with ANI calculations using Skani to quickly identify species based on NCBI and GTDB taxonomies. The tool evaluates performance in species identification and uncovers potential mislabelling in public databases. DFAST_QC is designed to be efficient and user-friendly, suitable for large-scale genomic studies.
The link to access DFAST_QC is here.
The article introduces SProtFP, a machine learning-based method for functional classification of small open reading frames (smORFs) in prokaryotes. It uses artificial neural networks trained on physicochemical descriptors to classify smORFs into categories like antitoxin, bacteriocin, and RNA-binding proteins. The method was benchmarked with an average ROC-AUC of 0.92 and was applied to annotate bacterial isolates from the human gut microbiome. SProtFP aims to facilitate large-scale functional annotation of smORFs, especially when sequence homology is low.
SProtFP is freely available at?here.
The article introduces PSAURON, a tool for assessing protein annotation quality across various species using a machine learning model. PSAURON assigns scores to coding DNA or protein sequences, reflecting their likelihood of being genuine protein-coding regions. The tool evaluates genome-wide protein annotations and identifies potentially spurious proteins. Validation shows PSAURON's effectiveness and correlation with established measures of protein quality.
PSAURON is freely available at?here.
?? Community News
Researchers have discovered that Structural Maintenance of Chromosomes (SMC) proteins, which are crucial for chromosome transmission during cell replication, can switch directions. This finding challenges the previous belief that these proteins only move in one direction. This discovery could have implications for understanding diseases like cancer and neurodegenerative disorders.?
Seeing the unseen: New method reveals 'hyperaccessible' window in freshly replicated DNA | PHYS.ORG?
The article discusses a new method developed by researchers to identify “hyperaccessible” regions in freshly replicated DNA. These regions are more open and accessible to cellular machinery, which could have significant implications for understanding DNA replication and gene regulation. The method called RASAM (Replication-Aware Single-molecule Accessibility Mapping) uses advanced imaging techniques to visualize these regions, providing new insights into the dynamics of DNA replication and its role in cellular processes.?
A European collaboration has successfully provided genetic diagnoses for over 500 patients with previously undiagnosed rare disorders. The study, published in Nature Medicine, involved reanalysing genetic data from 6,004 families across Europe. This effort has improved the rate of genetic diagnosis for rare diseases, which often have a significant genetic component.?
Mount Sinai researchers developed an AI tool that predicts cancer patients' responses to immune checkpoint inhibitor therapy using routine blood tests and clinical data. The tool, SCORPIO, offers a cost-effective and accessible solution for oncologists.?
Researchers have successfully determined the structure of the Nipah virus polymerase complex using cryo-electron microscopy (cryo-EM). This breakthrough provides critical insights into the virus's replication mechanism and could aid in developing targeted antiviral treatments.?
?? Upcoming Events
This webinar, organized by EMBL-EBI, will delve into the features of?PDBe-KB Ligand Pages and provide guidance on how to use them to uncover scientific insights about small molecules in the PDB.??
?? Educational Corner
This blog post explores how to teach R specifically for cell biologists, rather than a general audience. It emphasizes the importance of reproducibility, automation, and creating publication-quality graphics. The post outlines a typical workflow from experiment to figure, using R to process and visualize data from cell biology experiments.?
This blog post offers practical tips for creating Quarto?revealjs?presentations, such as adjusting slide size, optimizing code chunk width, and using the?formatR?package for tidy code. It also covers previewing slides on different screen sizes and setting global options in the YAML header.
This blog post introduces the {flowchart} package, which simplifies creating flowcharts in R using a?tidyverse?workflow. It highlights the package's ability to automatically adapt to data, eliminating the need for manual parameter adjustments, and demonstrates its use with the built-in?safo?dataset.
The article discusses how to interact with locally hosted Large Language Models (LLMs) in R using the?ellmer?package and LM Studio. The post also touches on the challenges of using LLM APIs in R.?
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