David C. Wedge

Scalable spatial DNA sequencing from archival tissue maps copy number subclones

This paper introduces ARMS DNAseq, a scalable spatial genomic assay that maps copy number subclones in archival tissue, revealing tumor evolution and subclone associations with morphology and transcriptomic features.

Identification and Validation of a Previously Missed Mutational Signature in Colorectal Cancer

The paper identifies and validates a previously missed mutational signature in microsatellite-stable colorectal cancer, showing it is distinct from known signatures and not caused by canonical DNA repair defects.

A fast numerical integration scheme for clonal expansion processes on graphs

This paper introduces a numerical integration scheme to compute survival probabilities in clonal expansion processes on arbitrary graphs, demonstrating its application to parameter inference in a graphical model.

Examining the Role of Extrachromosomal DNA in Lung Cancer

This study examines ecDNA in lung cancer, finding it in 18.9% of patients and associating it with worse survival and genomic instability.

Replication fork directionality reveals how structural variants arise under replication stress

The paper identifies a novel mechanism for large tandem duplications in cancer by analyzing replication fork directionality and develops a classifier to distinguish SV phenotypes based on replication features.

Proteomics-constrained deconvolution reveals spatial cell-type programs in tumours

PISTACHIO improves spatial cell-type deconvolution in tumours using proteomics constraints and non-negative matrix factorization.

Whole genome sequencing of endometrial cancer identifies novel subgroups, drivers, and actionable alterations

This study uses whole genome sequencing of endometrial cancers to identify novel subgroups, drivers, and actionable alterations, improving precision medicine approaches.

Whole-genome pre-amplification as a viable approach for genomic screening of FFPE-derived DNA samples

This study evaluates DLMDA for improving DNA yield from FFPE samples but finds it reduces CNA sensitivity.

Revealing the Drivers Underlying Distinct Evolutionary Trajectories in Lung Adenocarcinoma

This study identifies three distinct evolutionary trajectories in lung adenocarcinomas using whole-genome sequencing, revealing that some never-smoking tumors follow smoking-like paths driven by KRAS mutations.

Methylation reprogramming associated with aggressive prostate cancer and ancestral disparities

The paper investigates DNA methylation differences in prostate cancer across African, European, and Asian ancestries, finding ancestry-driven methylation patterns linked to disease aggressiveness in African tumors.

Deciphering lung adenocarcinoma evolution and the role of LINE-1 retrotransposition

This study analyzes 1024 lung adenocarcinomas to identify evolutionary patterns and mutational mechanisms, revealing distinct trajectories linked to smoking, ancestry, and retrotransposition.

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

The paper identifies two lung cancer subtypes defined by APOBEC mutagenesis levels and shows their association with different genetic mutations, aging, and immune responses.

Uncovering novel mutational signatures by de novo extraction with SigProfilerExtractor

SigProfilerExtractor is a tool for de novo mutational signature extraction that outperforms existing methods and identifies four novel signatures, including one linked to tobacco smoking.

Crowd-sourced benchmarking of single-sample tumour subclonal reconstruction

The paper benchmarks 31 subclonal reconstruction algorithms on simulated tumours, finding that algorithm choice significantly impacts performance and no single algorithm excels across all tasks.

Benchmarking small-variant genotyping in polyploids

The paper benchmarks small-variant genotyping in polyploids using Octopus and other tools on synthetic and real datasets, finding Octopus has 25% fewer errors on average.

Whole-genome analysis of Nigerian patients with breast cancer reveals ethnic-driven somatic evolution and distinct genomic subtypes

The paper analyzes whole-genome data from Nigerian breast cancer patients, identifying ethnic-driven somatic evolution and distinct genomic subtypes associated with African ancestry.

Germline loss-of-function variants in the base-excision repair gene MBD4 cause a Mendelian recessive syndrome of adenomatous colorectal polyposis and acute myeloid leukaemia

A unified haplotype-based method for accurate and comprehensive variant calling

Octopus is a haplotype-based variant caller that accurately detects germline and somatic variants in diverse scenarios, including tumours and parent-offspring trios.

Genomic copy number predicts oesophageal cancer years before transformation

This study shows genomic copy number changes can predict oesophageal cancer up to 10 years before diagnosis, enabling earlier treatment and reduced unnecessary monitoring.

Multi-site clonality analyses uncovers pervasive subclonal heterogeneity and branching evolution across melanoma metastases

The paper analyzes whole-genome sequencing data from melanoma metastases to show that branched evolution is common and that subclonal heterogeneity is prevalent in metastatic melanoma.

The genomic and epigenomic evolutionary history of papillary renal cell carcinomas

This study examines intratumor heterogeneity and clonal evolution in papillary renal cell carcinomas using whole-genome sequencing and DNA methylation data, revealing distinct patterns of genomic and epigenomic evolution across subtypes.

Genetic and Epigenetic Intratumor Heterogeneity Impacts Prognosis of Lung Adenocarcinoma

This study quantifies genetic and epigenetic intratumor heterogeneity in lung adenocarcinoma and links it to poor prognosis.

Genomic evidence supports a clonal diaspora model for metastases of esophageal adenocarcinoma

The paper uses whole genome sequencing and phylogenetic analysis to show that metastases in esophageal adenocarcinoma spread rapidly through a clonal diaspora model.

Creating Standards for Evaluating Tumour Subclonal Reconstruction

This study develops quantitative metrics and simulated datasets to evaluate subclonal reconstruction methods in tumours.

Correcting reference bias from the Illumina Isaac aligner enables analysis of cancer genomes

The paper identifies a bias in VAF estimates from the Illumina Isaac aligner and introduces FixVAF to correct it, improving cancer cell fraction analysis.

Copy number motifs expose genome instability type and predict driver events and disease outcome in breast cancer

The paper identifies copy number motifs in breast cancer genomes that predict disease outcome and driver events, outperforming existing clinical and genomic markers.

Pan-cancer analysis of whole genomes reveals driver rearrangements promoted by LINE-1 retrotransposition in human tumours

The paper analyzes somatic retrotransposition events in 2,954 cancer genomes, identifying L1 insertions as significant contributors to structural variations and oncogenesis.