Pheno-Ranker: a toolkit for comparison of phenotypic data stored in GA4GH standards and beyond.

Background: Phenotypic data comparison is essential for disease association studies, patient stratification, and genotype-phenotype correlation analysis. To support these efforts, the Global Alliance for Genomics and Health (GA4GH) established Phenopackets v2 and Beacon v2 standards for storing, sharing, and discovering genomic and phenotypic data. These standards provide a consistent framework for organizing biological data, simplifying their transformation into computer-friendly formats.

ONCOLINER: A new solution for monitoring, improving, and harmonizing somatic variant calling across genomic oncology centers.

The characterization of somatic genomic variation associated with the biology of tumors is fundamental for cancer research and personalized medicine, as it guides the reliability and impact of cancer studies and genomic-based decisions in clinical oncology. However, the quality and scope of tumor genome analysis across cancer research centers and hospitals are currently highly heterogeneous, limiting the consistency of tumor diagnoses across hospitals and the possibilities of data sharing and data integration across studies. With the aim of providing users with actionable and personalized recommendations for the overall enhancement and harmonization of somatic variant identification across research and clinical environments, we have developed ONCOLINER.

The Catalan initiative for the Earth BioGenome Project: contributing local data to global biodiversity genomics.

The Catalan Initiative for the Earth BioGenome Project (CBP) is an EBP-affiliated project network aimed at sequencing the genome of the >40 000 eukaryotic species estimated to live in the Catalan-speaking territories (Catalan Linguistic Area, CLA). These territories represent a biodiversity hotspot. While covering less than 1% of Europe, they are home to about one fourth of all known European eukaryotic species.

Multi-organ single-cell transcriptomics of immune cells uncovered organ-specific gene expression and functions.

Despite the wealth of publicly available single-cell datasets, our understanding of distinct resident immune cells and their unique features in diverse human organs remains limited. To address this, we compiled a meta-analysis dataset of 114,275 CD45+ immune cells sourced from 14 organs in healthy donors. While the transcriptome of immune cells remains relatively consistent across organs, our analysis has unveiled organ-specific gene expression differences (GTPX3 in kidney, DNTT and ACVR2B in thymus).

Machine learning and multi-omics data in chronic lymphocytic leukemia: the future of precision medicine?

Chronic lymphocytic leukemia is a complex and heterogeneous hematological malignancy. The advance of high-throughput multi-omics technologies has significantly influenced chronic lymphocytic leukemia research and paved the way for precision medicine approaches. In this review, we explore the role of machine learning in the analysis of multi-omics data in this hematological malignancy.

Convert-Pheno: A software toolkit for the interconversion of standard data models for phenotypic data.

Efficient sharing and integration of phenotypic data is crucial for advancing biomedical research and enhancing patient outcomes in precision medicine and public health. To achieve this, the health data community has developed standards to promote the harmonization of variable names and values. However, the use of diverse standards across different research centers can hinder progress.

Development of a novel streamlined workflow (AACRE) and database (inCREDBle) for genomic analysis of carbapenem-resistant Enterobacterales.

In response to the threat of increasing antimicrobial resistance, we must increase the amount of available high-quality genomic data gathered on antibiotic-resistant bacteria. To this end, we developed an integrated pipeline for high-throughput long-read sequencing, assembly, annotation and analysis of bacterial isolates and used it to generate a large genomic data set of carbapenemase-producing Enterobacterales (CPE) isolates collected in Spain. The set of 461 isolates were sequenced with a combination of both Illumina and Oxford Nanopore Technologies (ONT) DNA sequencing technologies in order to provide genomic context for chromosomal loci and, most importantly, structural resolution of plasmids, important determinants for transmission of antimicrobial resistance.

Genetic newborn screening and digital technologies: A project protocol based on a dual approach to shorten the rare diseases diagnostic path in Europe.

Since 72% of rare diseases are genetic in origin and mostly paediatrics, genetic newborn screening represents a diagnostic "window of opportunity". Therefore, many gNBS initiatives started in different European countries. Screen4Care is a research project, which resulted of a joint effort between the European Union Commission and the European Federation of Pharmaceutical Industries and Associations.

A chromosome-level reference genome for the common octopus, Octopus vulgaris (Cuvier, 1797).

Cephalopods are emerging animal models and include iconic species for studying the link between genomic innovations and physiological and behavioral complexities. Coleoid cephalopods possess the largest nervous system among invertebrates, both for cell counts and brain-to-body ratio. Octopus vulgaris has been at the center of a long-standing tradition of research into diverse aspects of cephalopod biology, including behavioral and neural plasticity, learning and memory recall, regeneration, and sophisticated cognition.

Germ line variants in patients with acute myeloid leukemia without a suspicion of hereditary hematologic malignancy syndrome.

Germ line predisposition in acute myeloid leukemia (AML) has gained attention in recent years because of a nonnegligible frequency and an impact on management of patients and their relatives. Risk alleles for AML development may be present in patients without a clinical suspicion of hereditary hematologic malignancy syndrome. In this study we investigated the presence of germ line variants (GVs) in 288 genes related to cancer predisposition in 47 patients with available paired, tumor-normal material, namely bone marrow stroma cells (n = 29), postremission bone marrow (n = 17), and saliva (n = 1).

Dissecting the Origin of Heterogeneity in Uterine and Ovarian Carcinosarcomas.

Unlabelled: Gynecologic carcinosarcomas (CS) are biphasic neoplasms composed of carcinomatous (C) and sarcomatous (S) malignant components. Because of their rarity and histologic complexity, genetic and functional studies on CS are scarce and the mechanisms of initiation and development remain largely unknown. Whole-genome analysis of the C and S components reveals shared genomic alterations, thus emphasizing the clonal evolution of CS.

A critical spotlight on the paradigms of FFPE-DNA sequencing.

In the late 19th century, formalin fixation with paraffin-embedding (FFPE) of tissues was developed as a fixation and conservation method and is still used to this day in routine clinical and pathological practice. The implementation of state-of-the-art nucleic acid sequencing technologies has sparked much interest for using historical FFPE samples stored in biobanks as they hold promise in extracting new information from these valuable samples. However, formalin fixation chemically modifies DNA, which potentially leads to incorrect sequences or misinterpretations in downstream processing and data analysis.

A global catalog of whole-genome diversity from 233 primate species.

The rich diversity of morphology and behavior displayed across primate species provides an informative context in which to study the impact of genomic diversity on fundamental biological processes. Analysis of that diversity provides insight into long-standing questions in evolutionary and conservation biology and is urgent given severe threats these species are facing. Here, we present high-coverage whole-genome data from 233 primate species representing 86% of genera and all 16 families.

The landscape of tolerated genetic variation in humans and primates.

Personalized genome sequencing has revealed millions of genetic differences between individuals, but our understanding of their clinical relevance remains largely incomplete. To systematically decipher the effects of human genetic variants, we obtained whole-genome sequencing data for 809 individuals from 233 primate species and identified 4.3 million common protein-altering variants with orthologs in humans.

The landscape of tolerated genetic variation in humans and primates.

Unlabelled: Personalized genome sequencing has revealed millions of genetic differences between individuals, but our understanding of their clinical relevance remains largely incomplete. To systematically decipher the effects of human genetic variants, we obtained whole genome sequencing data for 809 individuals from 233 primate species, and identified 4.3 million common protein-altering variants with orthologs in human.

Remote visualization of large-scale genomic alignments for collaborative clinical research and diagnosis of rare diseases.

The Solve-RD project objectives include solving undiagnosed rare diseases (RD) through collaborative research on shared genome-phenome datasets. The RD-Connect Genome-Phenome Analysis Platform (GPAP), for data collation and analysis, and the European Genome-Phenome Archive (EGA), for file storage, are two key components of the Solve-RD infrastructure. Clinical researchers can identify candidate genetic variants within the RD-Connect GPAP and, thanks to the developments presented here as part of joint ELIXIR activities, are able to remotely visualize the corresponding alignments stored at the EGA.

DNA methylation in human gastric epithelial cells defines regional identity without restricting lineage plasticity.

Background: Epigenetic modifications in mammalian DNA are commonly manifested by DNA methylation. In the stomach, altered DNA methylation patterns have been observed following chronic Helicobacter pylori infections and in gastric cancer. In the context of epigenetic regulation, the regional nature of the stomach has been rarely considered in detail.

The ulcerative colitis-associated gene FUT8 regulates the quantity and quality of secreted mucins.

Mucins are the main macrocomponents of the mucus layer that protects the digestive tract from pathogens. Fucosylation of mucins increases mucus viscoelasticity and its resistance to shear stress. These properties are altered in patients with ulcerative colitis (UC), which is marked by a chronic inflammation of the distal part of the colon.

A method for multiplexed full-length single-molecule sequencing of the human mitochondrial genome.

Methods to reconstruct the mitochondrial DNA (mtDNA) sequence using short-read sequencing come with an inherent bias due to amplification and mapping. They can fail to determine the phase of variants, to capture multiple deletions and to cover the mitochondrial genome evenly. Here we describe a method to target, multiplex and sequence at high coverage full-length human mitochondrial genomes as native single-molecules, utilizing the RNA-guided DNA endonuclease Cas9.