The genomic landscape of 2,023 colorectal cancers.

Colorectal carcinoma (CRC) is a common cause of mortality, but a comprehensive description of its genomic landscape is lacking. Here we perform whole-genome sequencing of 2,023 CRC samples from participants in the UK 100,000 Genomes Project, thereby providing a highly detailed somatic mutational landscape of this cancer. Integrated analyses identify more than 250 putative CRC driver genes, many not previously implicated in CRC or other cancers, including several recurrent changes outside the coding genome.

Kataegis associated mutational processes linked to adverse prostate cancer presentation in African men.

Kataegis, the focal hypermutation of single base substitutions (SBS) in tumour genomes, has received little attention with respect to prostate cancer (PCa) associated molecular and clinical features. Most notably, data is lacking with regards to this tumour evolutionary phenomenon and PCa racial disparities, with African men disproportionately impacted. Here through comparison between African (n = 109) and non-African (n = 79) whole genome sequenced treatment naïve primary tumours, using a single analytical workflow we assessed for shared and unique features of kataegis.

Analysis of 10,478 cancer genomes identifies candidate driver genes and opportunities for precision oncology.

Tumor genomic profiling is increasingly seen as a prerequisite to guide the treatment of patients with cancer. To explore the value of whole-genome sequencing (WGS) in broadening the scope of cancers potentially amenable to a precision therapy, we analysed whole-genome sequencing data on 10,478 patients spanning 35 cancer types recruited to the UK 100,000 Genomes Project. We identified 330 candidate driver genes, including 74 that are new to any cancer.

Crowd-sourced benchmarking of single-sample tumor subclonal reconstruction.

Subclonal reconstruction algorithms use bulk DNA sequencing data to quantify parameters of tumor evolution, allowing an assessment of how cancers initiate, progress and respond to selective pressures. We launched the ICGC-TCGA (International Cancer Genome Consortium-The Cancer Genome Atlas) DREAM Somatic Mutation Calling Tumor Heterogeneity and Evolution Challenge to benchmark existing subclonal reconstruction algorithms. This 7-year community effort used cloud computing to benchmark 31 subclonal reconstruction algorithms on 51 simulated tumors.

The mutagenic forces shaping the genomic landscape of lung cancer in never smokers.

Lung cancer in never smokers (LCINS) accounts for up to 25% of all lung cancers and has been associated with exposure to secondhand tobacco smoke and air pollution in observational studies. Here, we evaluate the mutagenic exposures in LCINS by examining deep whole-genome sequencing data from a large international cohort of 871 treatment-naïve LCINS recruited from 28 geographical locations within the Sherlock- study. mutations were 3.

AmplificationTimeR: an R package for timing sequential amplification events.

Motivation: Few methods exist for timing individual amplification events in regions of focal amplification. Current methods are also limited in the copy number states that they are able to time. Here we introduce AmplificationTimeR, a method for timing higher level copy number gains and inferring the most parsimonious order of events for regions that have undergone both single gains and whole genome duplication.

APOBEC shapes tumor evolution and age at onset of lung cancer in smokers.

APOBEC enzymes are part of the innate immunity and are responsible for restricting viruses and retroelements by deaminating cytosine residues. Most solid tumors harbor different levels of somatic mutations attributed to the off-target activities of APOBEC3A (A3A) and/or APOBEC3B (A3B). However, how APOBEC3A/B enzymes shape the tumor evolution in the presence of exogenous mutagenic processes is largely unknown.

Genomic evolution shapes prostate cancer disease type.

The development of cancer is an evolutionary process involving the sequential acquisition of genetic alterations that disrupt normal biological processes, enabling tumor cells to rapidly proliferate and eventually invade and metastasize to other tissues. We investigated the genomic evolution of prostate cancer through the application of three separate classification methods, each designed to investigate a different aspect of tumor evolution. Integrating the results revealed the existence of two distinct types of prostate cancer that arise from divergent evolutionary trajectories, designated as the Canonical and Alternative evolutionary disease types.

Intra-prostatic tumour evolution, steps in metastatic spread and histogenomic associations revealed by integration of multi-region whole-genome sequencing with histopathological features.

Background: Extension of prostate cancer beyond the primary site by local invasion or nodal metastasis is associated with poor prognosis. Despite significant research on tumour evolution in prostate cancer metastasis, the emergence and evolution of cancer clones at this early stage of expansion and spread are poorly understood. We aimed to delineate the routes of evolution and cancer spread within the prostate and to seminal vesicles and lymph nodes, linking these to histological features that are used in diagnostic risk stratification.

Chromothripsis orchestrates leukemic transformation in blast phase MPN through targetable amplification of .

Chromothripsis, the process of catastrophic shattering and haphazard repair of chromosomes, is a common event in cancer. Whether chromothripsis might constitute an actionable molecular event amenable to therapeutic targeting remains an open question. We describe recurrent chromothripsis of chromosome 21 in a subset of patients in blast phase of a myeloproliferative neoplasm (BP-MPN), which alongside other structural variants leads to amplification of a region of chromosome 21 in ∼25% of patients ('chr21amp').

Whole genome sequencing refines stratification and therapy of patients with clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the most common form of kidney cancer, but a comprehensive description of its genomic landscape is lacking. We report the whole genome sequencing of 778 ccRCC patients enrolled in the 100,000 Genomes Project, providing the most detailed somatic mutational landscape to date. We identify new driver genes, which as well as emphasising the major role of epigenetic regulation in ccRCC highlight additional biological pathways extending opportunities for drug repurposing.

Landscape of Genetic Alterations Underlying Hallmark Signature Changes in Cancer Reveals Aneuploidy-driven Metabolic Reprogramming.

Unlabelled: The hallmark signatures based on gene expression capture core cancer processes. Through a pan-cancer analysis, we describe the overview of hallmark signatures across tumor types/subtypes and reveal significant relationships between these signatures and genetic alterations. mutation exerts diverse changes, including increased proliferation and glycolysis, which are closely mimicked by widespread copy-number alterations.

Insecticidal Activity of Jatropha Extracts Against the Azalea Lace Bug, Stephanitis pyrioides (Hemiptera: Tingidae).

We assessed bioactivity of ethanolic extracts from 35 species of Jatropha L. against an ornamental plant pest, the azalea lace bug, Stephanitis pyrioides (Scott). Jatropha extracts were prepared by air-drying stem, root, or whole plant material, grinding the tissue into a fine powder, adding 70% ethanol, and then vacuum filtering the contents.

Uncovering novel mutational signatures by extraction with SigProfilerExtractor.

Mutational signature analysis is commonly performed in cancer genomic studies. Here, we present SigProfilerExtractor, an automated tool for extraction of mutational signatures, and benchmark it against another 13 bioinformatics tools by using 34 scenarios encompassing 2,500 simulated signatures found in 60,000 synthetic genomes and 20,000 synthetic exomes. For simulations with 5% noise, reflecting high-quality datasets, SigProfilerExtractor outperforms other approaches by elucidating between 20% and 50% more true-positive signatures while yielding 5-fold less false-positive signatures.

Electromyography as a surrogate for estimating metabolic energy expenditure during locomotion.

Minimizing metabolic energy expenditure (MEE) plays an important role in increasing mobility in people with locomotor disabilities, as movements that require high energy lead to less activity. Rehabilitation programs and devices use MEE to determine how effective they are, but using indirect calorimetry is limiting due to time delays and non-real-world conditions. Electromyography (EMG) offers insight into how muscles activate; thus, the purpose of this study was to develop a real-time MEE feedback system through the utilization of EMG signals.

Discovery of Niphimycin C from sp. nov. as a Promising Agrochemical Fungicide for Controlling Banana Wilt by Destroying the Mitochondrial Structure and Function.

Banana wilt caused by f. sp. () is the most destructive soil-borne fungal disease.