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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 …

Tumor phylogeography reveals block-shaped spatial heterogeneity and the mode of evolution in Hepatocellular Carcinoma

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 …

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 …

Genetic Load and Potential Mutational Meltdown in Cancer Cell Populations

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 …