Lineage tree analysis of immunoglobulin variable-region gene mutations in autoimmune diseases: chronic activation, normal selection

Autoimmune diseases show high diversity in the affected organs, clinical manifestations and disease dynamics. Yet they all share common features, such as the ectopic germinal centers found in many affected tissues. Lineage trees depict the diversification, via somatic hypermutation (SHM), of immunoglobulin variable-region (IGV) genes. We previously developed an algorithm for quantifying the graphical properties of IGV gene lineage trees, allowing evaluation of the dynamical interplay between SHM and antigen-driven selection in different lymphoid tissues, species, and disease situations. Here, we apply this method to ectopic GC B cell clones from patients with Myasthenia Gravis, Rheumatoid Arthritis, and Sjögren’s Syndrome, using data scaling to minimize the effects of the large variability due to methodological differences between groups. Autoimmune trees were found to be significantly larger relative to normal controls. In contrast, comparison of the measurements for tree branching indicated that similar selection pressure operates on autoimmune and normal control clones

Ecometric Modelling of Limb Proportions and Vegetation Index Among Non-Human Primates in South America

Ecometric modelling assesses how the functional morphology of ecogeographic communities relates to environmental variables. This improves understanding of how the interaction between organism and environment can result in morphological adaptation. This technique has mainly been used to model paleoenvironments, but has the capacity to aid conservation by quantifying how communities are structured through space and time. Here, we test the relationship between limb proportions and the habitat ecology of South American non-human primates. There is a significant but weak fit between limb proportions and habitat, consistent with the environment exerting weak selective pressure on limb proportions. In contrast, body size and phylogeny are strongly correlated with IMI. Together, these findings suggest that habitat was a selection pressure that shaped how New World monkeys' limb proportions evolved but this selection pressure was secondary to that of body size. Research into these functional relationships is important not only to improve scientific understanding of their evolutionary pathways but also in order to aid their protection by informing conservation practices. Ensuring these species have the capacity to move with their niche is an immediate concern, as they face mounting pressure due to deforestation of the Amazon basin

Quantifying evolutionary constraints on B cell affinity maturation

The antibody repertoire of each individual is continuously updated by the evolutionary process of B cell receptor mutation and selection. It has recently become possible to gain detailed information concerning this process through high-throughput sequencing. Here, we develop modern statistical molecular evolution methods for the analysis of B cell sequence data, and then apply them to a very deep short-read data set of B cell receptors. We find that the substitution process is conserved across individuals but varies significantly across gene segments. We investigate selection on B cell receptors using a novel method that side-steps the difficulties encountered by previous work in differentiating between selection and motif-driven mutation; this is done through stochastic mapping and empirical Bayes estimators that compare the evolution of in-frame and out-of-frame rearrangements. We use this new method to derive a per-residue map of selection, which provides a more nuanced view of the constraints on framework and variable regions.Comment: Previously entitled "Substitution and site-specific selection driving B cell affinity maturation is consistent across individuals

Detecting and quantifying causal associations in large nonlinear time series datasets

Identifying causal relationships and quantifying their strength from observational time series data are key problems in disciplines dealing with complex dynamical systems such as the Earth system or the human body. Data-driven causal inference in such systems is challenging since datasets are often high dimensional and nonlinear with limited sample sizes. Here, we introduce a novel method that flexibly combines linear or nonlinear conditional independence tests with a causal discovery algorithm to estimate causal networks from large-scale time series datasets. We validate the method on time series of well-understood physical mechanisms in the climate system and the human heart and using large-scale synthetic datasets mimicking the typical properties of real-world data. The experiments demonstrate that our method outperforms state-of-the-art techniques in detection power, which opens up entirely new possibilities to discover and quantify causal networks from time series across a range of research fields

Development of boldness and docility in yellow-bellied marmots

Peer reviewedPostprin

Nose Heat: Exploring Stress-induced Nasal Thermal Variability through Mobile Thermal Imaging

Automatically monitoring and quantifying stress-induced thermal dynamic information in real-world settings is an extremely important but challenging problem. In this paper, we explore whether we can use mobile thermal imaging to measure the rich physiological cues of mental stress that can be deduced from a person's nose temperature. To answer this question we build i) a framework for monitoring nasal thermal variable patterns continuously and ii) a novel set of thermal variability metrics to capture a richness of the dynamic information. We evaluated our approach in a series of studies including laboratory-based psychosocial stress-induction tasks and real-world factory settings. We demonstrate our approach has the potential for assessing stress responses beyond controlled laboratory settings