Although mitochondrial DNA (mtDNA) variants hold promise as endogenous barcodes for tracking human cell lineages, their efficacy as reliable lineage markers is hindered by the complex dynamics of mtDNA in somatic tissues. Here, we utilized …
Phylodynamics inference (PI) is a powerful approach for quantifying population dynamics and evolutionary trajectories of natural species based on phylogenetic trees. The emergence of single-cell lineage tracing technologies now enables the …
Esophageal squamous cell carcinoma (ESCC) is a poor-prognostic cancer type with extensive intra- and inter-patient heterogeneity in both genomic variations and tumor microenvironment (TME). However, the patterns and drivers of spatial genomic and …
Solid tumors are complex ecosystems with heterogeneous 3D structures, but the spatial intra-tumor heterogeneity (sITH) at the macroscopic (i.e., whole tumor) level is under-explored. Using a phylogeographic approach, we sequence genomes and …
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.