Single-cell RNA sequencing (scRNA-seq) is a powerful approach for studying cellular differentiation, but accurately tracking cell fate transitions can be challenging, especially in disease conditions. Here we introduce PhyloVelo, a computational …
Mitochondria are essential organelles in eukaryotic cells that provide critical support for energetic and metabolic homeostasis. Although the elimination of pathogenic mitochondrial DNA (mtDNA) mutations in somatic cells has been observed, the …
Cancer is an evolutionary process fueled by genetic or epigenetic alterations in the genome. Understanding the evolutionary dynamics that are operative at different stages of tumor progression might inform effective strategies in early detection, diagnosis, and treatment of cancer.
The timing of cancer metastasis has implications for treatment and prevention. Traditional forward-time views of metastasis assume it occurs late during evolution. However, looking backward in time reveals metastasis often occurs prior to clinical …
Analysis of WES data from 457 paired primary tumor and metastatic samples in three cancer types reveals early metastatic seeding and the impact of drug treatment on metastatic clonal evolution.
Analysis of genomic data within a spatial tumor growth model and statistical inference framework indicates that early disseminated cells commonly seed metastases while the carcinoma is clinically undetectable.
Genomic changes observed across treatment may result from either clonal evolution or geographically disparate sampling of heterogeneous tumors. Here we use computational modeling based on analysis of fifteen primary breast tumors and find that …
Large genomes with elevated mutation rates are prone to accumulating deleterious mutations more rapidly than natural selection can purge (Muller’s ratchet). As a consequence, it may lead to the extinction of small populations. Relative to most …
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The advent and application of next-generation sequencing (NGS) technologies to tumor genomes has reinvigorated efforts to understand clonal evolution. Although tumor progression has traditionally been viewed as a gradual stepwise process, recent …