Source Themes

Clonal expansion dictates the efficacy of mitochondrial lineage tracing in single cells

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 …

Single-cell phylodynamic inference of tissue development and tumor evolution with scPhyloX

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 …

Immune-tumor interaction dictates spatially directed evolution of esophageal squamous cell carcinoma

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 …

PhyloVelo enhances transcriptomic velocity field mapping using monotonically expressed genes

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 …

A genetic bottleneck of mitochondrial DNA during human lymphocyte development

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 …

Delineating the longitudinal tumor evolution using organoid models

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.

Looking backward in time to define the chronology of metastasis

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 …

Multi-cancer analysis of clonality and the timing of systemic spread in paired primary tumors and metastases

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.

Quantitative evidence for early metastatic seeding in colorectal cancer

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.

Clonal replacement and heterogeneity in breast tumors treated with neoadjuvant HER2-targeted therapy

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 …