Genome informatics articles within Nature Communications

Zymoseptoria tritici is an important fungal pathogen of wheat which has spread globally. Here, the authors perform genomic analyses on a collection of ~1100 Z. tritici samples from 42 countries to describe its global spread and elucidate mechanisms of adaptation to different environmental conditions.

The genetic basis of spider major ampullate (Ma) gland silk production remains unknown. Hu et al. unveil a molecular atlas of this gland for the golden orb-weaving spider combining genome assembly and multiomics, revealing the single-cell spatial architecture of silk production in the Ma gland.

Pachytene Piwi-interacting RNAs (piRNAs) expressed in mammalian germ lines are abundant, but their evolution and function are not fully understood. Here, the authors find that pachytene piRNA loci are hotspots of structural variation, which underlies rapid piRNA birth, divergence, and loss.

Long-read sequencing is promising for the detection of structural variants (SVs), which requires algorithms with high sensitivity and precision. Here, the authors develop DeBreak, an algorithm for comprehensive and accurate SV detection in long-read sequencing data across different platforms, which outperforms other SV callers.

Genomes usually contain multiple chromosomes. The paper reports on GALA, a computational framework for chromosome-based sequencing data separation and gap-free de novo assembly. It allows integration of different sources of data.

Analysis of a large number of Ribo-seq datasets and genomic alignments led to detection of novel non-AUG proteoforms. Unexpectedly the number of non-AUG proteoforms identified with Ribo-seq greatly exceeds those with strong phylogenetic support.

The power of pangenomic graphs to improve genetic mapping is still unclear. Here, the authors demonstrate its value in identification of genetic variants associated with disease resistance traits in melon using PanPipes, a pangenome construction and low-coverage genotype-by-sequencing pipeline.

Predicting topological structures from Hi-C data provides insight into comprehending gene expression and regulation. Here, the authors present RefHiC, an attention-based deep learning framework that leverages a reference panel of Hi-C datasets to assist topological structure annotation from a given study sample.

Here the authors show that transposable element-mediated rearrangements impact more than 500 kbp of an average human genome, are a source of individual variation, a substrate for evolutionary change, and can occur through diverse mechanisms.

Consensus sequence-based methods for self-correction of long-read sequencing data are affected by biases that can mask true variants characterizing little-covered or low-frequency haplotypes. Here, to address this issue, the authors develop a variation graph-based method for performing haplotype-aware self-correction of long reads.

Here the authors develop CAMMiQ, a combinatorial optimization approach that utilizes variable length, “unique” and “doubly-unique” genomic segments, showing improves identification and quantification of distinct microbes in metagenomic sequence data.

Monitoring of co-infections of SARS-CoV-2 variants is important to evaluate their clinical impact and the risk of emergence of recombinants. Here, the authors develop and validate a methodological pipeline to detect co-infections and apply it to samples from France in early 2022, when Delta and Omicron were co-circulating.

Reference genomes for gut microbiomes help unravel microbial “dark matter” and serve as valuable resource for disease-focused studies. Here, the authors perform short and long read metagenomics and metagenome-assembled genomes analyses to profile the gut microbiome of Southeast Asian populations, revealing significant species and strain-level diversity, with thousands of previously uncharacterized biosynthetic gene clusters.

DNA damage has been implicated in aging and neurodegeneration. Here, the authors develop a bioinformatic method to detect deletions in single neuron genome sequences and reveal an increased burden of somatic deletions during aging and in DNA repair disorders.

The function of many microbial genes is yet unknown. Here the authors repurposed natural language processing algorithms to explore “gene semantics” and infer function for thousands of genes with defense and secretion systems found to have the most discovery potential.

Identifying structural variants (SVs) under positive selection in cancer is challenging. Here, the authors develop CSVDriver, a method that computes SV breakpoint proximity and the contribution of elements such as topologically associating domains, and identifies loci that show signs of positive selection and contain known and putative drivers.

Many archived tumour samples are stored as formalin-fixed and paraffin-embedded (FFPE) blocks, but this treatment can impact downstream genomics analyses. Here, the authors derive the mutational signatures of formalin on the cancer genome, and present FFPEsig, an algorithm that can distinguish and correct FFPE mutational signatures in archived cancer samples.

As the scale of single-cell genomics experiments grows into the millions, the computational requirements to process this data are beyond the reach of many. Here the authors present Scarf, a modularly designed Python package that makes the analysis workflow highly memory efficient such that even the largest existing datasets can be analyzed on an average modern laptop.

Graph-based genome reference representations have seen significant development, motivated by the inadequacy of the current human genome reference to represent the diverse genetic information from different human populations and its inability to maintain the same level of accuracy for non-European ancestries. Here the authors present the case for iteratively augmenting tailored genome graphs for targeted populations and demonstrate this approach on the whole-genome samples of African ancestry.

Previous work has investigated selection in the coding genome, but it is not as well characterized in the non-coding genome. By analyzing rare variants in 70k genome sequences from gnomAD, the authors detect very strong purifying selection ("ultraselection”) across the human genome, finding it in some microRNAs and coding sequences but generally rare in regulatory sequences.

A critical task in spatial transcriptomics analysis is to understand inherently spatial relationships among cells. Here, the authors present a deep learning framework to integrate spatial and transcriptional information, spatially extending pseudotime and revealing spatiotemporal organization of cells.

It is unclear if the molecular profiles of pancreatic ductal adenocarcinoma (PDAC) preclinical models remain stable during propagation. Here, the authors characterise clonal evolution throughout propagation in PDAC cell lines and a patient-derived organoid using single-cell genomics, transcriptomics and epigenomics.

Low-copy repeats cover up to 5% of the human genome and are prone to extensive copy number variation. Here, the authors present a novel computational method to estimate paralog-specific copy number of such regions using whole-genome sequencing.

Pangenomes have a number of advantages over linear reference assemblies. Here the authors use bovine haplotype-resolved assemblies to show that structural variant-based pangenomes are consistent regardless of sequence platform, assembler, or coverage, suggesting that rigid protocols may not be required.

Biobanks of genetic data have been primarily in European populations, which gives us an incomplete understanding of complex traits across populations. Here, the authors initiate the Westlake BioBank for Chinese (WBBC) pilot project with 4,535 whole genome sequences and 5,841 high-density genotypes from China, characterizing large-scale genomic variation in Chinese populations.

Predicting drug responses in cancer patients requires robust computational frameworks. Here, the authors develop an integral genomic signature —iGenSig— approach to predict drug responses using multi-omics data from tumour samples, and validate this approach using genomic datasets from multiple clinical studies.

The role of genome folding in the heritability and evolvability of structural variations is not well understood. Here the authors investigate the impact of the three-dimensional genome topology of germ cells in the formation and transmission of gross structural genomic changes detected from comparing whole-genome sequences of 14 rodent species.

Piwi-interacting RNAs are small RNAs produced by processing of long precursor transcripts. Here the authors report that precursor cleavage typically occurs at positions corresponding to stop codons and that this pattern is conserved across mammals.

Here the authors digested chromatin with DNA fragmentation factor (DFF) prior to chromatin immunoprecipitation (DFF-ChIP) to depict transcription complex interactions with neighboring nucleosomes in cells. Applying this method to human cytomegalovirus (HMCV)-infected cells, they find that the viral genome is underchromatinized, leading to fewer transcription complex interactions with nucleosomes.

Anopheles mosquitoes are vectors of human malaria, and better understanding of them has implications for public health. Here, the authors apply Hi-C, FISH, RNA-seq, and ChIP-seq techniques to comprehensively characterize chromatin architecture and its evolutionary dynamics in five Anopheles species.

Plasmodium malariae is a cause of malaria in humans and related species have been identified in non-human primates. Here, the authors use genomic analyses to establish that human P. malariae arose from a host switch of an ape parasite whilst a species infecting New World monkeys can be traced to a reverse zoonosis.

Genetic variants affecting the consensus splicing motifs can alter binding of spliceosomal components and induce mis-splicing. Here, the authors develop a method, showing that ranking the most common recurring mis-splicing events in public RNA-Seq data can predict the activation of cryptic-donors.

Use of antimicrobials in livestock contributes to development of antimicrobial resistance but there are few large-scale surveillance studies. Here, the authors describe E. coli surveillance in pig farms in China, reporting high levels of multidrug-resistance across all mainland provinces.

Here, Johansen et al. develop an approach, Phages from Metagenomics Binning (PHAMB), that allows the binning of thousands of viral genomes directly from bulk metagenomics data, while simultaneously enabling clustering of viral genomes into accurate taxonomic viral populations, unveiling viral-microbial host interactions in the gut.

Lab-based surveillance of Shigella has traditionally been based on serotyping but increasing availability of whole genome sequencing could enable higher resolution typing. Here, the authors apply a core genome multilocus sequence typing scheme to Shigella sequence data and describe its population structure.

The exceptionally long-lived naked mole-rat is characterized by the lack of increased mortality with aging. Here the authors perform epigenetic studies to show that naked mole-rats epigenetically age despite their non-increasing mortality rate.

A lot of cancer patients are not responsive to anti-PD1 therapy. Here, the authors develop a network approach to identify genes, pathways and potential therapeutic combinations and develop an MHC-I gene immunoscore associated with tumour response to anti-PD1.

Breast cancer heterogeneity and tumour evolutionary trajectories remain largely unknown among women of African ancestry. Here, the authors perform whole genome and transcriptome sequencing of Nigerian breast cancer patients and identify unique evolutionary phenomena.

@melkebir @psashittal et al. develop a graph-based method for the assembly of discontinuous transcripts produced in Coronaviruses and other Nidovirales, enabling the discovery of transcriptional changes missed by existing methods.

Subclonal deconvolution in cancer sequencing data is a complex task, and the optimal tools to use are unclear. Here, the authors systematically benchmark subclonal deconvolution pipelines with a comprehensive set of simulated tumour genomes and identify the best-performing methods.

Historical interbreeding between Neanderthals and humans should leave signatures of historical demographics in modern human genomes. Analysing the size distribution of Neanderthal fragments in non-African genomes suggests consistent differences in the generation interval across Eurasia, and that this could explain mutational spectrum variation.

Duplications of gene segments can allow novel physiological adaptations to evolve. A detailed analysis of the TCAF gene family in primates and archaic humans suggest rapid duplication and diversification in this gene family is associated with cold or dietary adaptations.

Alternative polyadenylation regulates localization, half-life and translation of mRNA isoforms. Here the authors investigate alternative polyadenylation using single cell RNA sequencing data from mouse embryos and identify 3’-UTR isoforms that are regulated across cell types and developmental time.

Grouping T-cell receptors (TCRs) by sequence similarity could lead to new immunological insights. Here, the authors propose a tool that allows the rapid clustering of millions of TCR sequences, identifying TCRs potentially associated with the response to cancer, infectious and autoimmune diseases.

Despite being a common congenital facial anomaly, the genetic etiology of craniofacial microsomia (CFM) is not well understood. Here, the authors use exome and genome sequencing of 146 individuals with CFM to identify haploinsufficient variants in SF3B2 as a prevalent underlying cause.

Existing long-read de novo assembly methods can partially, but not completely, separate strains. Here, the authors develop Strainberry, a metagenome assembly bioinformatic pipeline that exclusively uses longread data to accurately separate and reconstruct strain genomes from single-sample low-complexity microbiomes.

Variable number tandem repeats (VNTRs) are difficult to analyze by short-read sequencing in disease studies. Here, the authors describe a VNTR mapping strategy for short-read analyses using a repeat pangenome graph. This method will help elucidate the contribution of VNTRs to diversity and disease.

Identification of transposable element (TE) insertions from whole genome sequencing data remains challenging. Here the authors developed a comprehensive TE insertion detection algorithm xTea that can be applied to both short-read and long-read sequencing data.

Traditional methods to identify genomic regions identical-by-descent (IBD) do not scale well to biobank-level datasets. Here, the authors describe a new IBD algorithm, iLASH, which uses LocAlity-Sensitive Hashing to provide rapid IBD estimation when applied to the PAGE and UK Biobank datasets.