A comparison of clustering models for inference of T cell receptor antigen specificity.

The vast potential sequence diversity of TCRs and their ligands has presented an historic barrier to computational prediction of TCR epitope specificity, a holy grail of quantitative immunology. One common approach is to cluster sequences together, on the assumption that similar receptors bind similar epitopes. Here, we provide the first independent evaluation of widely used clustering algorithms for TCR specificity inference, observing some variability in predictive performance between models, and marked differences in scalability. Despite these differences, we find that different algorithms produce clusters with high degrees of similarity for receptors recognising the same epitope. Our analysis strengthens the case for use of clustering models to identify signals of common specificity from large repertoires, whilst highlighting scope for improvement of complex models over simple comparators.

Can we predict T cell specificity with digital biology and machine learning?

Recent advances in machine learning and experimental biology have offered breakthrough solutions to problems such as protein structure prediction that were long thought to be intractable. However, despite the pivotal role of the T cell receptor (TCR) in orchestrating cellular immunity in health and disease, computational reconstruction of a reliable map from a TCR to its cognate antigens remains a holy grail of systems immunology. Current data sets are limited to a negligible fraction of the universe of possible TCR-ligand pairs, and performance of state-of-the-art predictive models wanes when applied beyond these known binders. In this Perspective article, we make the case for renewed and coordinated interdisciplinary effort to tackle the problem of predicting TCR-antigen specificity. We set out the general requirements of predictive models of antigen binding, highlight critical challenges and discuss how recent advances in digital biology such as single-cell technology and machine learning may provide possible solutions. Finally, we describe how predicting TCR specificity might contribute to our understanding of the broader puzzle of antigen immunogenicity.

multiSyncPy: A Python package for assessing multivariate coordination dynamics.

In order to support the burgeoning field of research into intra- and interpersonal synchrony, we present an open-source software package: multiSyncPy. Multivariate synchrony goes beyond the bivariate case and can be useful for quantifying how groups, teams, and families coordinate their behaviors, or estimating the degree to which multiple modalities from an individual become synchronized. Our package includes state-of-the-art multivariate methods including symbolic entropy, multidimensional recurrence quantification analysis, coherence (with an additional sum-normalized modification), the cluster-phase 'Rho' metric, and a statistical test based on the Kuramoto order parameter. We also include functions for two surrogation techniques to compare the observed coordination dynamics with chance levels and a windowing function to examine time-varying coordination for most of the measures. Taken together, our collation and presentation of these methods make the study of interpersonal synchronization and coordination dynamics applicable to larger, more complex and often more ecologically valid study designs. In this work, we summarize the relevant theoretical background and present illustrative practical examples, lessons learned, as well as guidance for the usage of our package - using synthetic as well as empirical data. Furthermore, we provide a discussion of our work and software and outline interesting further directions and perspectives. multiSyncPy is freely available under the LGPL license at: https://github.com/cslab-hub/multiSyncPy , and also available at the Python package index.

Multidisciplinary care of the dying adolescent.

The adolescent at the end of life poses a unique combination of challenges resulting from the collision of failing health with a developmental trajectory meant to lead to attainment of personal independence. Because virtually all spheres of the dying adolescent's life are affected, optimal palliative care for these young persons requires a multidisciplinary team whose members have a good understanding of their complementary roles and a shared commitment to providing well-coordinated care. Members of the team include the physician (to initiate and coordinate palliative care management); the nurse (to work collaboratively with the physician and adolescent, especially through effective patient advocacy); the psychologist (to assess and manage the patient's neurocognitive and emotional status); the social worker (to assess and optimize support networks); the chaplain (to support the adolescent's search for spiritual meaning); and the child life specialist (to facilitate effective communication in preparing for death). A crucial area for dying adolescents is medical decision making, where the full range of combined support is needed. By helping the young person continue to develop personal autonomy, the multidisciplinary team will enable even the dying adolescent to experience dignity and personal fulfillment.