bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/037770

Statistics of Cellular Evolution in Leukemia: Allelic Variations in Patient Trajectories Based on Immune Repertoire Sequencing

Hong Gao·Chunlin Wang·Junhee Seok·Marcus W Feldman·Wenzhong Xiao
View original source ↗Export metadata ↓

Abstract

The evolution of a cancer system consisting of cancer clones and normal cells is a complex dynamic process with multiple interacting factors including clonal expansion, somatic mutation, and sequential selection. As a typical example, in patients with chronic lymphocytic leukemia (CLL), a monoclonal population of transformed B cells expands to dominate the B cell population in the peripheral blood and bone marrow. This expansion of transformed B cells suggests that they might evolve through processes distinct from those of normal B cells. Recent advances in next generation sequencing enable the high-throughput identification and tracking of individual B cell clones through sequencing of the V-D-J junction segments of the immunoglobulin heavy chain (IGH). Here we developed a statistical approach to modeling cellular evolution of the immune repertoire. Adapting the infinitely many alleles model from population genetics, we studied abnormalities occurring in the immune repertoire of patients as substantial deviations from the null model. The Ewens sampling test (EST) distinguished the immune repertoires of CLL patients with imminent relapse from healthy controls and patients in sustained remission. Extensive simulations based on sequencing data showed that EST is sensitive in detecting cancer-related derangements of the IGH repertoire. In addition, we suggest two potentially useful parameters: the rate at which donors B cell clones enter the circulation and the average time to regenerate a transplanted immune repertoire, both of which help to distinguish relapsing CLL patients from those in sustained remission and provide additional information about the dynamics of immune reconstitution in the latter patients. We anticipate that our models and statistics will be useful in diagnosis and prognosis of leukemia, and may be adapted for application to other diseases related to adaptive immunity.

Explore related subjects

Evolutionary BiologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Hong Gao, Chunlin Wang, Junhee Seok, Marcus W Feldman, Wenzhong Xiao. 2016-01-25. Statistics of Cellular Evolution in Leukemia: Allelic Variations in Patient Trajectories Based on Immune Repertoire Sequencing. https://doi.org/10.1101/037770

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2019

Evolutionary successful strategies in a transparent iterated Prisoner's Dilemma

A Transparent game is a game-theoretic setting that takes action visibility into account. In each round, depending on the relative timing of their actions, players have a certain probability to see their partners choice before making their own decision. This probability is determined by the level of transparency. At the two extremes, a game with zero transparency is equivalent to the classical simultaneous game, and a game with maximal transparency corresponds to a sequential game. Despite the prevalence of intermediate transparency in many everyday interactions such scenarios have not been sufficiently studied. Here we consider a transparent iterated Prisoners dilemma (iPD) and use evolutionary simulations to investigate how and why the success of various strategies changes with the level of transparency. We demonstrate that non-zero transparency greatly reduces the set of successful memory-one strategies compared to the simultaneous iPD. For low and moderate transparency the classical "Win - Stay, Lose - Shift" (WSLS) strategy is the only evolutionary successful strategy. For high transparency all strategies are evolutionary unstable in the sense that they can be easily counteracted, and, finally, for maximal transparency a novel "Leader-Follower" strategy outperforms WSLS. Our results provide a partial explanation for the fact that the strategies proposed for the simultaneous iPD are rarely observed in nature, where high levels of transparency are common.

Evolutionary Biology↗
bioRxiv2019

Spontaneous whole-genome duplication restores fertility in interspecific hybrids

Interspecies hybrids often show advantages over parents but suffer from reduced fertility, which can sometimes be overcome through sexual reproduction that sorts out incompatibilities. Sex is however inefficient due to the low viability or fertility of hybrid offspring and thus limits their evolutionary potential. Mitotic cell division could be an alternative to fertility recovery in facultative sexual species. To test this, we evolved under relaxed selection more than 600 diploid yeast hybrids between species that span 100,000 to 15 M years of divergence. We find that hybrids can recover fertility spontaneously and rapidly through whole-genome duplication. These events occurred in both hybrids between young and well-established species. Our results show that the instability of hybrid ploidy is a spontaneous path to fertility recovery. One Sentence SummaryPloidy changes potentiate hybrid speciation by leading to fertility recovery.

Evolutionary Biology↗
bioRxiv2016

Using the Price equation to analyze multi-level selection on the reproductive policing mechanism of bacterial plasmids

The replication control system of non-conjugative bacterial plasmids constitutes a simple and elegant example of a reproductive policing mechanism that moderates competition in the intra-cellular replication pool and establishes a mutually beneficial partnership among plasmids within a bacterial host and between plasmids and their hosts. The emergence of these partnerships is a product of the conflict between the evolutionary interests of hosts, who seek to maximize their growth rates within the population, and plasmids, who seek to maximize their growth rates within hosts. We employ a multi-scale computational model describing the growth, division and death of hosts, as well as the independent replication of plasmids within hosts, in order to investigate the implications of this conflict for the evolution of the plasmid replication parameters. We apply the multi-level form of the Price equation in order to quantify and elucidate the various selective pressures that drive the evolution of plasmid replication control. Our analysis shows how the evolution of the constituent components of the plasmid replication control system are shaped by selection acting at the level of hosts and the level of plasmids. In addition, we calculate finer-grained selective pressures that are attributed to atomic plasmid-related events (such as intra-cellular replication and plasmid loss due to host death) and demonstrate their special role at the early stages of the evolution of policing. Our approach constitutes a novel application of the Price equation for discerning and discussing the synergies between the levels of selection given the availability of a mechanistic model for the generation of the systems dynamics. We show how the Price equation, particularly in its multi-level form, can provide significant insight by quantifying the relative importance of the various selective forces that shape the evolution of policing in bacterial plasmids.

Evolutionary Biology↗