HGVS Nomenclature 2024: improvements to community engagement, usability, and computability.

Background: The Human Genome Variation Society (HGVS) Nomenclature is the global standard for describing and communicating variants in DNA, RNA, and protein sequences in clinical and research genomics. This manuscript details recent updates to the HGVS Nomenclature, highlighting improvements in governance, community engagement, website functionality, and underlying implementation of the standard.

Methods: The HGVS Variant Nomenclature Committee (HVNC) now operates under the Human Genome Organization (HUGO), facilitating broader community feedback and collaboration with related standards organizations.

Accessible viral metagenomics for public health and clinical domains with Jovian.

The integration of next-generation sequencing into clinical diagnostics and surveillance initiatives is impeded by the lack of data analysis pipelines that align with privacy legislation and laboratory certification protocols. To address these challenges, we developed Jovian, an open-source, virus-focused, metagenomic analysis workflow for Illumina data. Jovian generates scaffolds enriched with pertinent annotations, including taxonomic classification, combined with metrics needed for quality assessment (coverage depth, average GC content, localization of open reading frames, minority single nucleotide polymorphisms), and incorporates host and disease metadata.

Long-term wastewater monitoring of SARS-CoV-2 viral loads and variants at the major international passenger hub Amsterdam Schiphol Airport: A valuable addition to COVID-19 surveillance.

Wastewater-based epidemiological surveillance at municipal wastewater treatment plants has proven to play an important role in COVID-19 surveillance. Considering international passenger hubs contribute extensively to global transmission of viruses, wastewater surveillance at this type of location may be of added value as well. The aim of this study is to explore the potential of long-term wastewater surveillance at a large passenger hub as an additional tool for public health surveillance during different stages of a pandemic.

Regional reemergence of a SARS-CoV-2 Delta lineage amid an Omicron wave detected by wastewater sequencing.

The implementation and integration of wastewater-based epidemiology constitutes a valuable addition to existing pathogen surveillance systems, such as clinical surveillance for SARS-CoV-2. In the Netherlands, SARS-CoV-2 variant circulation is monitored by performing whole-genome sequencing on wastewater samples. In this manuscript, we describe the detection of an AY.

Metagenomic Surveillance of Viral Gastroenteritis in a Public Health Setting.

Norovirus is the primary cause of viral gastroenteritis (GE). To investigate norovirus epidemiology, there is a need for whole-genome sequencing and reference sets consisting of complete genomes. To investigate the potential of shotgun metagenomic sequencing on the Illumina platform for whole-genome sequencing, 71 reverse transcriptase quantitative PCR (RT-qPCR) norovirus positive-feces (threshold cycle [], <30) samples from norovirus surveillance within The Netherlands were subjected to metagenomic sequencing.

A Boolean algebra for genetic variants.

Motivation: Beyond identifying genetic variants, we introduce a set of Boolean relations, which allows for a comprehensive classification of the relations of every pair of variants by taking all minimal alignments into account. We present an efficient algorithm to compute these relations, including a novel way of efficiently computing all minimal alignments within the best theoretical complexity bounds.

Results: We show that these relations are common, and many non-trivial, for variants of the CFTR gene in dbSNP.

compareMS2 2.0: An Improved Software for Comparing Tandem Mass Spectrometry Datasets.

It has long been known that biological species can be identified from mass spectrometry data alone. Ten years ago, we described a method and software tool, compareMS2, for calculating a distance between sets of tandem mass spectra, as routinely collected in proteomics. This method has seen use in species identification and mixture characterization in food and feed products, as well as other applications.

Whole genome sequencing and the application of a SNP panel reveal primary evolutionary lineages and genomic variation in the lion (Panthera leo).

Background: Previous phylogeographic studies of the lion (Panthera leo) have improved our insight into the distribution of genetic variation, as well as a revised taxonomy which now recognizes a northern (Panthera leo leo) and a southern (Panthera leo melanochaita) subspecies. However, existing whole range phylogeographic studies on lions either consist of very limited numbers of samples, or are focused on mitochondrial DNA and/or a limited set of microsatellites. The geographic extent of genetic lineages and their phylogenetic relationships remain uncertain, clouded by massive sampling gaps, sex-biased dispersal and incomplete lineage sorting.

FAIR Genomes metadata schema promoting Next Generation Sequencing data reuse in Dutch healthcare and research.

The genomes of thousands of individuals are profiled within Dutch healthcare and research each year. However, this valuable genomic data, associated clinical data and consent are captured in different ways and stored across many systems and organizations. This makes it difficult to discover rare disease patients, reuse data for personalized medicine and establish research cohorts based on specific parameters.

Adenine base editing of the polyadenylation signal for targeted genetic therapy in facioscapulohumeral muscular dystrophy.

Facioscapulohumeral muscular dystrophy (FSHD) is caused by chromatin relaxation of the D4Z4 repeat resulting in misexpression of the D4Z4-encoded gene in skeletal muscle. One of the key genetic requirements for the stable production of full-length mRNA in skeletal muscle is a functional polyadenylation signal (ATTAAA) in exon three of that is used in somatic cells. Base editors hold great promise to treat DNA lesions underlying genetic diseases through their ability to carry out specific and rapid nucleotide mutagenesis even in postmitotic cells such as skeletal muscle.

Situational optimization function analysis: An ideal performance analysis inspired on Lewin's equation.

This study presents the situational optimization function analysis (SOFA) and has three aims. First, to develop a Bayesian implementation of SOFA. Second, to compare this implementation with three other maximum likelihood-based models in their accuracy to estimate true scores.

Fecal Microbiota Transplantation Influences Procarcinogenic Escherichia coli in Recipient Recurrent Clostridioides difficile Patients.

Background & Aims: Patients with multiple recurrent Clostridioides difficile infection (rCDI) have a disturbed gut microbiota that can be restored by fecal microbiota transplantation (FMT). Despite extensive screening, healthy feces donors may carry bacteria in their intestinal tract that could have long-term health effects, such as potentially procarcinogenic polyketide synthase-positive (pks) Escherichia coli. Here, we aim to determine whether the pks abundance and persistence of pksE coli is influenced by pks status of the donor feces.

Mutalyzer 2: next generation HGVS nomenclature checker.

Motivation: Unambiguous variant descriptions are of utmost importance in clinical genetic diagnostics, scientific literature and genetic databases. The Human Genome Variation Society (HGVS) publishes a comprehensive set of guidelines on how variants should be correctly and unambiguously described. We present the implementation of the Mutalyzer 2 tool suite, designed to automatically apply the HGVS guidelines so users do not have to deal with the HGVS intricacies explicitly to check and correct their variant descriptions.

A catalogue of 863 Rett-syndrome-causing MECP2 mutations and lessons learned from data integration.

Rett syndrome (RTT) is a rare neurological disorder mostly caused by a genetic variation in MECP2. Making new MECP2 variants and the related phenotypes available provides data for better understanding of disease mechanisms and faster identification of variants for diagnosis. This is, however, currently hampered by the lack of interoperability between genotype-phenotype databases.

Coronavirus discovery by metagenomic sequencing: a tool for pandemic preparedness.

Introduction: The SARS-CoV-2 pandemic of 2020 is a prime example of the omnipresent threat of emerging viruses that can infect humans. A protocol for the identification of novel coronaviruses by viral metagenomic sequencing in diagnostic laboratories may contribute to pandemic preparedness.

Aim: The aim of this study is to validate a metagenomic virus discovery protocol as a tool for coronavirus pandemic preparedness.

Comprehensive diagnostics of acute myeloid leukemia by whole transcriptome RNA sequencing.

Acute myeloid leukemia (AML) is caused by genetic aberrations that also govern the prognosis of patients and guide risk-adapted and targeted therapy. Genetic aberrations in AML are structurally diverse and currently detected by different diagnostic assays. This study sought to establish whole transcriptome RNA sequencing as single, comprehensive, and flexible platform for AML diagnostics.

Taxonomic classification and abundance estimation using 16S and WGS-A comparison using controlled reference samples.

The assessment of microbiome biodiversity is the most common application of metagenomics. While 16S sequencing remains standard procedure for taxonomic profiling of metagenomic data, a growing number of studies have clearly demonstrated biases associated with this method. By using Whole Genome Shotgun sequencing (WGS) metagenomics, most of the known restrictions associated with 16S data are alleviated.

Dutch genome diagnostic laboratories accelerated and improved variant interpretation and increased accuracy by sharing data.

Each year diagnostic laboratories in the Netherlands profile thousands of individuals for heritable disease using next-generation sequencing (NGS). This requires pathogenicity classification of millions of DNA variants on the standard 5-tier scale. To reduce time spent on data interpretation and increase data quality and reliability, the nine Dutch labs decided to publicly share their classifications.

Archival, paleopathological and aDNA-based techniques in leprosy research and the case of Father Petrus Donders at the Leprosarium 'Batavia', Suriname.

Objective: We assessed whether Petrus Donders (died 1887), a Dutch priest who for 27 years cared for people with leprosy in the leprosarium Batavia, Suriname, had evidence of Mycobacterium (M.) leprae infection. A positive finding of M.

BacTag - a pipeline for fast and accurate gene and allele typing in bacterial sequencing data based on database preprocessing.

Background: Bacteria carry a wide array of genes, some of which have multiple alleles. These different alleles are often responsible for distinct types of virulence and can determine the classification at the subspecies levels (e.g.

Validity evidence of two short scales measuring the Big Five personality factors.

The objective of this study was to obtain evidence of the convergent and factor validity of the Reduced Scale of Big Five Personality Factors (ER5FP), with 20 items, and of the Reduced Inventory of Big Five Personality Factors (IGFP-5R), with 32 items. The two Brazilian scales were administered to 554 participants aged 16-69 years (M = 30.6, SD = 8.

Annotating Transcriptional Effects of Genetic Variants in Disease-Relevant Tissue: Transcriptome-Wide Allelic Imbalance in Osteoarthritic Cartilage.

Objective: Multiple single-nucleotide polymorphisms (SNPs) conferring susceptibility to osteoarthritis (OA) mark imbalanced expression of positional genes in articular cartilage, reflected by unequally expressed alleles among heterozygotes (allelic imbalance [AI]). We undertook this study to explore the articular cartilage transcriptome from OA patients for AI events to identify putative disease-driving genetic variation.

Methods: AI was assessed in 42 preserved and 5 lesioned OA cartilage samples (from the Research Arthritis and Articular Cartilage study) for which RNA sequencing data were available.

Short hypervariable microhaplotypes: A novel set of very short high discriminating power loci without stutter artefacts.

Since two decades, short tandem repeats (STRs) are the preferred markers for human identification, routinely analysed by fragment length analysis. Here we present a novel set of short hypervariable autosomal microhaplotypes (MH) that have four or more SNPs in a span of less than 70 nucleotides (nt). These MHs display a discriminating power approaching that of STRs and provide a powerful alternative for the analysis;1;is of forensic samples that are problematic when the STR fragment size range exceeds the integrity range of severely degraded DNA or when multiple donors contribute to an evidentiary stain and STR stutter artefacts complicate profile interpretation.

Brain Transcriptomic Analysis of Hereditary Cerebral Hemorrhage With Amyloidosis-Dutch Type.

Hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D) is an early onset hereditary form of cerebral amyloid angiopathy (CAA) caused by a point mutation resulting in an amino acid change (NP_000475.1:p.Glu693Gln) in the amyloid precursor protein (APP).

Critical points for an accurate human genome analysis.

Next-generation sequencing is radically changing how DNA diagnostic laboratories operate. What started as a single-gene profession is now developing into gene panel sequencing and whole-exome and whole-genome sequencing (WES/WGS) analyses. With further advances in sequencing technology and concomitant price reductions, WGS will soon become the standard and be routinely offered.