Search

This systematic review and meta-analysis of 149 randomized controlled trials finds that behavioral and psychosocial interventions outperform medications in improving core autism symptoms, while study design and context strongly influence reported treatment effects.

Using active and passive genomic surveillance, researchers observed the rapid spread of high pathogenicity avian influenza H5N1 D1.1 viruses in wild birds during the 2024 migratory season, which coincided with detection in humans, but did not identify mammalian adaptive markers in viruses from wild birds.

Genome-wide analysis shows European dogs existed by 14,200 years ago, were already genetically distinct, received less Neolithic Southwest Asian admixture than humans did and contributed substantially to later European dogs.

From 2014–2017, marine heatwaves caused global mass coral bleaching, where the corals lose their symbiotic algae. The authors find, this event exceeded the severity of all prior global bleaching events in recorded history, with approximately half the world’s reefs bleaching and 15% experiencing substantial mortality.

In wildlife tagging, stress from capture and handling can alter post- release behavior and potentially study interpretations. This study of 42 mammal species shows that these effects diminish within 4–7 days, and quicker for animals in high human activity areas indicating adaptation to disturbance.

Many tumours exhibit hypoxia (low oxygen) and hypoxic tumours often respond poorly to therapy. Here, the authors quantify hypoxia in 1188 tumours from 27 cancer types, showing elevated hypoxia links to increased mutational load, directing evolutionary trajectories.

There’s an emerging body of evidence to show how biological sex impacts cancer incidence, treatment and underlying biology. Here, using a large pan-cancer dataset, the authors further highlight how sex differences shape the cancer genome.

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

Chromosomal instability occurs frequently in cancer, making it an attractive therapeutic target. Here, the authors identify KIF18A as a targetable vulnerability of cancer cells with chromosomal instability and target this using VLS-1272, a selective KIF18A inhibitor.

The SARS-CoV-2 virus has been documented to transmit between humans and animals, providing opportunities for viral reservoirs. Here, the authors show SARS-CoV-2 lineages in free-ranging white-tailed deer across the United States, long after the lineages had declined in human populations.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

In somatic cells the mechanisms maintaining the chromosome ends are normally inactivated; however, cancer cells can re-activate these pathways to support continuous growth. Here, the authors characterize the telomeric landscapes across tumour types and identify genomic alterations associated with different telomere maintenance mechanisms.

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

Whole-genome sequencing data from more than 2,500 cancers of 38 tumour types reveal 16 signatures that can be used to classify somatic structural variants, highlighting the diversity of genomic rearrangements in cancer.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

Analysis of cancer genome sequencing data has enabled the discovery of driver mutations. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium the authors present DriverPower, a software package that identifies coding and non-coding driver mutations within cancer whole genomes via consideration of mutational burden and functional impact evidence.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

Some cancer patients first present with metastases where the location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.

The characterization of 4,645 whole-genome and 19,184 exome sequences, covering most types of cancer, identifies 81 single-base substitution, doublet-base substitution and small-insertion-and-deletion mutational signatures, providing a systematic overview of the mutational processes that contribute to cancer development.

In this study the authors consider the structural variants (SVs) present within cancer cases of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. They report hundreds of genes, including known cancer-associated genes for which the nearby presence of a SV breakpoint is associated with altered expression.

Cancers evolve as they progress under differing selective pressures. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, the authors present the method TrackSig the estimates evolutionary trajectories of somatic mutational processes from single bulk tumour data.

Fine-mapping of causal variants and integration of epigenetic and chromatin conformation data identify likely target genes for 150 breast cancer risk regions.

Over 170 susceptibility loci have been identified by genome-wide association studies in breast cancer. Here, the authors interrogated the role of risk-associated variants from non-breast tissue, and using expression quantitative trait loci, identify potential target genes of known breast cancer susceptibility variants, as well as 11 regions not previously known to be associated with breast cancer risk.

Efficient, large-scale genomic analysis is facilitated on the cloud by a computational tool with error-diagnosing and self-healing capabilities.

Similarities in cancers can be studied to interrogate their etiology. Here, the authors use genome-wide association study summary statistics from six cancer types based on 296,215 cases and 301,319 controls of European ancestry, showing that solid tumours arising from different tissues share a degree of common germline genetic basis.

Oestrogen negative breast cancer is associated with a poor prognosis. In this study, the authors perform a meta-analysis of 11 breast cancer genome-wide association studies and identify four new loci associated with oestrogen negative breast cancer risk. These findings may aid in stratifying patients in the clinic.

A transcriptome-wide association study identifies associations of genetically predicted gene expression with breast cancer risk. This analysis finds 48 candidate genes implicated in breast cancer susceptibility, including 14 at novel loci.

Narcolepsy has genetic and environmental risk factors, but the specific genetic risk loci and interaction with environmental triggers are not well understood. Here, the authors identify genetic loci for narcolepsy, suggesting infection as a trigger and dendritic and helper T cell involvement.

Genome-wide CRISPR knockout and activation screens in human lung epithelial cells with endogenous expression of the SARS-CoV-2 entry factors ACE2 and TMPRSS2 identify mucins as key host factors restricting viral infection.

Breast cancer risk for BRCA1/BRCA2 mutation carriers varies depending on other genetic factors. Here, the authors perform a case-only genome-wide association study and highlight novel loci associated with breast cancer risk for BRCA1/BRCA2 mutation carriers.

In breast cancer the contribution of different genetic variants to disease heritability is complex and not fully understood. Here, the authors present a network-based analysis in 84,567 patients studying ~7.3 million variants, identifying gene modules associated with breast cancer survival.

Comprehensive integration of gene expression with epigenetic features is needed to understand the transition of kidney cells from health to injury. Here, the authors integrate dual single nucleus RNA expression and chromatin accessibility, DNA methylation, and histone modifications to decipher the chromatin landscape of the kidney in reference and adaptive injury cell states, identifying a transcription factor network of ELF3, KLF6, and KLF10 which regulates adaptive repair and maladaptive failed repair.

Analysis of whole-genome sequencing data across 2,658 tumors spanning 38 cancer types shows that chromothripsis is pervasive, with a frequency of more than 50% in several cancer types, contributing to oncogene amplification, gene inactivation and cancer genome evolution.

Analysis of mitochondrial genomes (mtDNA) by using whole-genome sequencing data from 2,658 cancer samples across 38 cancer types identifies hypermutated mtDNA cases, frequent somatic nuclear transfer of mtDNA and high variability of mtDNA copy number in many cancers.

In this study the authors identify a possible link between the gene FAM222A and brain atrophy. The protein it encodes is found to accumulate in plaques seen in Alzheimer’s disease, and functional analysis suggests it interacts with amyloid-beta.

Genome-wide analysis identifies 32 loci associated with breast cancer susceptibility, accounting for estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade.

Roger Milne and colleagues conduct a genome-wide association study for estrogen receptor (ER)-negative breast cancer combined with BRCA1 mutation carriers in a large cohort. They identify ten new risk variants and find high genetic correlation between breast cancer risk for BRCA1 mutation carriers and risk of ER-negative breast cancer in the general population.

Association analysis identifies 65 new breast cancer risk loci, predicts target genes for known risk loci and demonstrates a strong overlap with somatic driver genes in breast tumours.