A single-cell landscape of high-grade serous ovarian cancer.

Malignant abdominal fluid (ascites) frequently develops in women with advanced high-grade serous ovarian cancer (HGSOC) and is associated with drug resistance and a poor prognosis. To comprehensively characterize the HGSOC ascites ecosystem, we used single-cell RNA sequencing to profile ~11,000 cells from 22 ascites specimens from 11 patients with HGSOC. We found significant inter-patient variability in the composition and functional programs of ascites cells, including immunomodulatory fibroblast sub-populations and dichotomous macrophage populations.

Multiplicative fitness, rapid haplotype discovery, and fitness decay explain evolution of human MHC.

The major histocompatibility complex (MHC) is a central component of the vertebrate immune system and hence evolves in the regime of a host-pathogen evolutionary race. The MHC is associated with quantitative traits which directly affect fitness and are subject to selection pressure. The evolution of haplotypes at the MHC HLA (HLA) locus is generally thought to be governed by selection for increased diversity that is manifested in overdominance and/or negative frequency-dependent selection (FDS).

Modeling coverage gaps in haplotype frequencies via Bayesian inference to improve stem cell donor selection.

Regardless of sampling depth, accurate genotype imputation is limited in regions of high polymorphism which often have a heavy-tailed haplotype frequency distribution. Many rare haplotypes are thus unobserved. Statistical methods to improve imputation by extending reference haplotype distributions using linkage disequilibrium patterns that relate allele and haplotype frequencies have not yet been explored.

HLA class I haplotype diversity is consistent with selection for frequent existing haplotypes.

The major histocompatibility complex (MHC) contains the most polymorphic genetic system in humans, the human leukocyte antigen (HLA) genes of the adaptive immune system. High allelic diversity in HLA is argued to be maintained by balancing selection, such as negative frequency-dependent selection or heterozygote advantage. Selective pressure against immune escape by pathogens can maintain appreciable frequencies of many different HLA alleles.

Population Growth Combined with Wide Offspring Distributions can Increase Fixation Rate and Reduce Genetic Diversity.

Genetic diversity grows with the population size in most neutral evolution models. Empirical evidence of large populations with limited diversity has been proposed to be due either to genetic bottlenecks or to selection. An alternative explanation is that the limited diversity is a result of rare reproduction events.

Estimate of within population incremental selection through branch imbalance in lineage trees.

Incremental selection within a population, defined as limited fitness changes following mutation, is an important aspect of many evolutionary processes. Strongly advantageous or deleterious mutations are detected using the synonymous to non-synonymous mutations ratio. However, there are currently no precise methods to estimate incremental selection.