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SeqControl uses 15 quality metrics of high-throughput sequencing experiments to predict how much sequencing is needed to reach a desired depth of coverage.

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.

Benchmarking of tumor subclonal reconstruction algorithms finds that interalgorithm variability overwhelms intertumor variability and identifies key quality metrics.

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.

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.

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.

Genomic analyses of localized, non-indolent prostate cancer identify recurrent aberrations that can predict relapse, and also highlight differences between early prostate cancer and metastatic, castration-resistant disease.

Paul Boutros, Robert Bristow and colleagues report a molecular analysis of the spatial heterogeneity of clinically localized, multifocal prostate cancer. They find that multifocal tumors are highly heterogeneous, and they identify a novel recurrent amplification of MYCL1.

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.

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.

BafilomycinA1 is an autophagy inhibitor, presumably owing to its blocking effect on the lysosomal proton pump V-ATPase. Here the authors show that V-ATPase-deficient lysosomes can still fuse with autophagosomes, showing that lysosomal acidification and fusion are two separable, independent events.

Accurate and actionable biomarkers that integrate diverse molecular, functional and clinical information hold great promise in precision medicine. Here, the authors develop SIMMS, a method for pathway-based cross-disease biomarker discovery.

Men that carrierBRCA2germline mutations are at risk of developing prostate cancer. Here, the authors analyse the genomes of prostate cancer from these individuals and demonstrate increased genomic instability in comparison to sporadic prostate cancer.

Transcriptome-wide m⁶A RNA methylation profile in 162 primary prostate tumors identifies m⁶A association with prognostic clinical features and disease aggression.

Molecular recorders based on kinase activity-dependent protein labeling track specific kinase activities to understand their link to cellular phenotypes in heterogeneous cell populations and in vivo.

Despite the known role of telomere length in cancer, its association with genomic features remains unclear. Here, the authors integrate telomere length, genomics, transcriptomics and proteomics in localized prostate cancer and reveal links between telomere maintenance, disease drivers and clinical outcomes.

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.

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.

DNA double-stranded breaks threaten genome stability. Here, the authors show that transcript RNA serves as a repair template in human cells and identify Polζ as a key factor in RNA-templated DSB repair. This process can lead to intron deletion, resulting in a mutational signature in cancer genomes.

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.

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.

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.

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.

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.

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.

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.

Biomarkers of prostate cancer metastasis have been difficult to determine with confidence. Here the authors analyse mutation prevalence in 1844 prostate cancers and show that ZNRF3 loss is enriched in metastatic, castration-resistant prostate cancer and associated with metastasis of localized disease.

In prostate cancer, the role of mutations in the maternally-inherited mitochondrial genome are not well known. Here, the authors demonstrate frequent, age-dependent mitochondrial mutation in prostate cancer. Strong links between mitochondrial and nuclear mutational profiles are associated with clinical aggressivity.

The paper describes a Genome in a Bottle benchmark for the X and Y chromosomes enabled by complete chromosome assemblies. This benchmark enables users to evaluate small variant accuracy in challenging repetitive regions of the sex chromosomes.

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.

Analysis of signatures of hypoxia in more than 8,000 tumors from 19 cancer types identifies hypoxia-driven mutation signatures and dysregulation of microRNAs.

The transcriptomic profile of tumour-adjacent cells provides important information about tumour context but its clinical utility is unclear. Here, in breast cancer, Fox et al. show that the mRNA abundances of tumour and tumour-adjacent cells hold prognostic information.

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.

The heterogeneity underlying cancer organoid phenotypes is not yet well understood. Here, the authors develop an imaging analysis assay for high throughput phenotypic screening of colorectal organoids that allows to define specific morphological changes that occur following different drug treatments.

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.

moPepGen enables the detection of peptides across species, proteases and technologies.

Ageing is a known risk factor in the development of cancers, but its association with molecular alterations is not fully explored. Here, the authors analyse pan-cancer age-associated molecular alterations in datasets from the TCGA, PCAWG and AACR-GENIE projects and identify prognostic biomarkers.

The impact of variant calling algorithms on the analysis of intra-tumour heterogeneity has not been properly quantified. Here the authors measure the variability of 22 pipelines with different variant callers and clustering algorithms for subclonal reconstruction to inform future analyses.

Urine can be used to easily analyse the health of patients. Here, the authors identify proteins in urinary extracellular vesicles that distinguish prostate cancer from benign lesions.

Proteomic technologies are capable of identifying thousands of proteins in biological samples, but biomarker applications are lagging. Here the authors use Multiple Reaction Monitoring Mass Spectrometry to delineate peptide signatures that accurately distinguish between defined prostate cancer patient risk groups.

Giafaglione et al. define metabolic regulation of prostate epithelial lineage identity and show that modulation of lactate metabolism alters response to antiandrogen therapy.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

The first report of the ICGC-TCGA DREAM Somatic Mutation Calling Challenge introduces the BAMSurgeon tool for accurate tumor simulation and reports the performance of 248 submissions in calling single-nucleotide variants from three pairs of synthetic tumor–normal genome benchmarks.