variant calling

Beyond Delta Masses: MS Andrea Directly Resolves Combinatorial Peptide Modifications in Open Searches

MS Andrea, a tag-filtered open search engine, scores and localizes up to four Unimod modifications per peptide-spectrum match, with identification counts competitive with MSFragger and Sage.

Phylogenomic screening reveals idsA2 loss conferring nitroimidazole cross-resistance in Mycobacterium tuberculosis

A length- and mutation-load-corrected homoplasy screen of 1,813 MDR-TB genomes flags idsA2; its loss raises pretomanid MIC fourfold, delamanid and ethambutol twofold, via isoprenoid flux redirection.

vardictcpp: A C++ reimplementation of VarDict variant caller

An AI-assisted C++17 port of VarDictJava gives byte-identical calls on five exome samples while running 3.7-4.8 times faster on one core and needing 8-17 times less memory.

Biobank-scale genotyping of Robertsonian translocations reveals hidden structural variation on the human acrocentric chromosomes

Short-read genomes can flag Robertsonian translocation carriers by counting rDNA distal junction (DJ) copies (8 rather than 10); UK Biobank screening found 583 candidates, 1 in 841.

A novel analysis pipeline and experimental design for measuring expanded repeat instability

Delta plots from targeted long-read data separate repeat instability frequency, expansion bias and change size; a single-clone assay (SCIA) shows FAN1 knockout raises expansion frequency but shrinks expansions.

Recomb-Mix Cloud: a cost-efficient and scalable cloud-friendly pipeline for local ancestry inference

On the All of Us workbench, a Recomb-Mix-based cloud pipeline runs whole-genome local ancestry inference for an estimated $0.01 per sample, versus $0.43 for FLARE and $4.58 for RFMix.

Patient-Derived Liver Cancer Organoids Reflect Tumor Biology and Their Growth Phenotype Correlates with Clinical Outcomes

Organoids grew from 13 of 27 resected hepatocellular carcinomas. The sequenced lines kept parental mutations, and solid rather than cystic growth marked shorter progression-free survival (HR 13.91).

Accurate ab initio gene prediction in eukaryotes with Tiberius in multiple clades

Extended Tiberius models outscore Helixer and ANNEVO on all 33 genomes from the five clades all three tools cover, and approach BRAKER3 accuracy in four clades without extrinsic evidence.

kamino: fast proteome-wide variant calling for amino acid phylogenomics

Proteome-wide variant calling builds amino acid phylogenomic alignments orders of magnitude faster than a BUSCO marker pipeline, with similar tree signal in three of four test taxa.

Gene conversion is a key driver of diversity hotspots in M. tuberculosis antigens and virulence-associated loci

Complete genomes from 151 clinical M. tuberculosis isolates show gene conversion between paralogs creating diversity hotspots in PE/PPE/ESX genes and T cell antigens, including PPE18.

Emergence of short-lived meningococci causing focal epidemics can be associated with gene transfer from carriage-associated Neisseria

A 21-case nightclub-linked meningococcal outbreak variant differed from its closest relatives by horizontal gene transfer from carriage-associated Neisseria, affecting iron acquisition and type IV pili genes.

PanGBank: a large-scale resource of precomputed microbial pangenomes built with PPanGGOLiN

Precomputed PPanGGOLiN pangenomes for over 4,600 prokaryotic species (Genome Taxonomy Database clusters), with plasticity regions and modules, downloadable via web, API and command line for projection onto new genomes.

Single-Cell Indel Detection Enhances Genetic Ancestry and Cellular Lineage Analysis

Monopogen-Indel calls germline indels from single-cell and single-nucleus RNA data at 73.0% (retina) and ~87% (ovarian cancer) WGS-validated precision, though no single-cell somatic indel matched a WGS somatic indel.

Parallel evolution under constraint shapes echinocandin resistance in Candida auris

Across 681 matched isolates and 22,388 genomes, high-level micafungin resistance in Candida auris arises through recurrent FKS1 hotspot mutations amid strong purifying selection, and FKS2 appears dispensable.

The Genomic Landscape of Post-Black Death Epidemics in Northern Europe and the Caucasus

Twenty-three new Yersinia pestis genomes from Scandinavia, the Netherlands, Iceland and Armenia extend the Second Plague Pandemic phylogeny, with the first Icelandic plague genome and eastward-spreading pestis secunda strains.

SVkhor: a unified framework for structural variant integration across long-read, short-read, and optical genome mapping data

SVkhor normalizes, merges and integrates long-read, short-read and optical-mapping structural variant calls; on HG002 it retained 98.6% of naive concatenation's true positives with 58.2% fewer false positives.

HPRC2: A human pangenome reference with near-complete coverage of common genetic variation

460 haplotypes from 230 genomes, selected to maximize common-variant coverage, capture 99.43% of All of Us common small variants and halve structurally unreliable regions and base errors versus HPRC1.

A global map for introgressed structural variation and selection in humans

Long-read phased assemblies from two Papuans plus 47 HPRC genomes map archaic introgressed structural variants, revealing 11 candidate archaic centromeres and 16 candidate adaptive SVs.

Biodistribution of mRNA vaccines in rats: Enrichment in injection site and lymph tissues and rapid clearance without tissue persistence

Three mRNA-LNP products sharing one lipid matrix show rat intramuscular biodistribution (injection site, lymph nodes, spleen) and rapid clearance, with no Spike accumulation after repeat dosing.

High-efficiency, transgene-free plant genome editing by viral delivery of an engineered TnpB

Tobacco rattle virus delivery of engineered ISDra2 variant eTnpBc and its guide RNA as a single transcript achieves up to 90% somatic and 100% heritable editing in Nicotiana benthamiana.

Helixer--de novo Prediction of Primary Eukaryotic Gene Models Combining Deep Learning and a Hidden Markov Model

Helixer, a hybrid convolutional/bLSTM network with a hidden Markov model post-processor, predicts eukaryotic primary gene models from DNA alone, outscoring GenemarkES and AUGUSTUS on most species.

Typhi Mykrobe: fast and accurate lineage identification and antimicrobial resistance genotyping directly from sequence reads for the typhoid fever agent Salmonella Typhi

Mykrobe k-mer panel genotypes Salmonella Typhi lineages, antimicrobial resistance (AMR) markers and plasmids from Illumina or nanopore reads, matching mapping-based lineage calls for 99.8% of genomes.

Complex genetic variation in nearly complete human genomes

Hybrid HiFi/ultra-long ONT assemblies of 65 diverse humans yield 130 haplotypes, 1,246 complete centromeres, and a pangenome panel enabling short-read genome inference at median QV 45.

Activation of Wnt/β-catenin signalling by mutually exclusive FBXW11 and CTNNB1 hotspot mutations drives salivary gland basal cell adenoma

Exome and transcriptome sequencing of salivary basal cell adenomas reveals a recurrent FBXW11 p.F517S mutation, exclusive with CTNNB1 p.I35T, together accounting for 94% of cases.

Synchronized long-read genome, methylome, epigenome, and transcriptome for resolving a Mendelian condition

Pooling Fiber-seq gDNA with concatenated MAS-Seq cDNA in one PacBio run gives phased genome, methylome, chromatin, and transcriptome, exposing four gene disruptions from one X;13 translocation.

MOIRE: A software package for the estimation of allele frequenciesand effective multiplicity of infection from polyallelic data

MOIRE, a Bayesian R package, jointly infers allele frequencies, multiplicity of infection (MOI) and within-host relatedness from SNP or polyallelic malaria genotypes, yielding a panel-portable effective MOI.

De novo variants in the non-coding spliceosomal snRNA gene RNU4-2 are a frequent cause of syndromic neurodevelopmental disorders

Mostly de novo variants in an 18 bp constrained region of U4 snRNA gene RNU4-2 cause a syndromic neurodevelopmental disorder, estimated to explain 0.41% of cases.

How low can you go? Short-read polishing of Oxford Nanopore bacterial genome assemblies

Roughly 25× short-read depth polishes nearly all residual errors in Nanopore-only bacterial assemblies; new '--careful' modes in Pypolca and Polypolish largely avoid introducing low-depth errors.

The variation and evolution of complete human centromeres

A second complete human centromere set (CHM1) plus 31 nonhuman primate centromeres reveals extensive α-satellite higher-order repeat variation, kinetochore repositioning, and saltatory emergence of new repeats.

Assigning mutational signatures to individual samples and individual somatic mutations with SigProfilerAssignment

SigProfilerAssignment refits known substitution, doublet, indel and copy-number mutational signatures to single samples and probabilistically to individual mutations, outperforming four refitting tools on 2,700 synthetic genomes.