Phys Sci Res Assoc, Academic Units
- Eigenvalues of neutral networks: Interpolating between hypercubes DISCRETE MATHEMATICS 2016; 339 (4): 1283-1290
- Obstruction of adaptation in diploids by recessive, strongly deleterious alleles PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2015; 112 (20): E2658-E2666
- Quantitative evolutionary dynamics using high-resolution lineage tracking NATURE 2015; 519 (7542): 181-?
Beyond genome sequencing: Lineage tracking with barcodes to study the dynamics of evolution, infection, and cancer
2014; 104 (6): 417-430
Evolving cellular communities, such as the gut microbiome, pathogenic infections, and cancer, consist of large populations of ~10(7)-10(14) cells. Because of their large population sizes, adaptation within these populations can be driven by many beneficial mutations that never rise above extremely low frequencies. Genome sequencing methods such as clonal, single cell, or whole population sequencing are poorly suited to detect these rare beneficial lineages, and, more generally, to characterize which mutations are most important to the population dynamics. Here, we introduce an alternative approach: high-resolution lineage tracking with DNA barcodes. In contrast to whole genome sequencing, lineage tracking can detect a beneficial mutation at an extremely low frequency within the population, and estimate its time of occurrence and fitness effect. Many lineage trajectories can be observed in parallel, allowing one to observe the population dynamics in exquisite detail. We describe some of the technical and analytical challenges to lineage tracking with DNA barcodes and discuss its applications to studies of evolution, infectious disease and cancer.
View details for DOI 10.1016/j.ygeno.2014.09.005
View details for Web of Science ID 000346059200006
View details for PubMedID 25260907