Computational strategies for dissecting the high-dimensional complexity of adaptive immune repertoires

The adaptive immune system recognizes antigens via an immense array of antigen-binding antibodies and T-cell receptors, the immune repertoire. The interrogation of immune repertoires is of high relevance for understanding the adaptive immune response in disease and infection (e.g., autoimmunity, cancer, HIV). Adaptive immune receptor repertoire sequencing (AIRR-seq) has driven the quantitative and molecular-level profiling of immune repertoires thereby revealing the high-dimensional complexity of the immune receptor sequence landscape. Several methods for the computational and statistical analysis of large-scale AIRR-seq data have been developed to resolve immune repertoire complexity in order to understand the dynamics of adaptive immunity. Here, we review the current research on (i) diversity, (ii) clustering and network, (iii) phylogenetic and (iv) machine learning methods applied to dissect, quantify and compare the architecture, evolution, and specificity of immune repertoires. We summarize outstanding questions in computational immunology and propose future directions for systems immunology towards coupling AIRR-seq with the computational discovery of immunotherapeutics, vaccines, and immunodiagnostics.Comment: 27 pages, 2 figure

Parental and Dentist Satisfaction with Primary Anterior Zirconia Crowns: A Case Series Analysis

This retrospective cohort study evaluated overall parental satisfaction of zirconia crowns (ZC) placed on primary maxillary anterior teeth with that of two independent, blinded dentists. 131 ZC placed in 37 children, aged 24.8–62.2 months (mean = 42.8), who had at least one recall visit a minimum of 6 months after placement were rated (average = 13.3). Crown colour match, crown contour and crown durability were evaluated by parents and compared to photographic evaluations of two independent raters. Overall parental satisfaction was also evaluated. The overall retention rate was 99.7% and parental satisfaction was 100%. Colour match was rated excellent by 84% of parents and 36% of dental evaluators. Crown contour was rated excellent by 97% of parents and 55% of dental evaluators. The length of follow-up had no effect on colour match or crown contour. ZC comprises an aesthetic and durable option for restoring carious primary maxillary incisors and were well-accepted by parents. Parents were less critical than dental evaluators of crown appearance

T cell receptor sequence clustering and antigen specificity

There has been increasing interest in the role of T cells and their involvement in cancer, autoimmune and infectious diseases. However, the nature of T cell receptor (TCR) epitope recognition at a repertoire level is not yet fully understood. Due to technological advances a plethora of TCR sequences from a variety of disease and treatment settings has become readily available. Current efforts in TCR specificity analysis focus on identifying characteristics in immune repertoires which can explain or predict disease outcome or progression, or can be used to monitor the efficacy of disease therapy. In this context, clustering of TCRs by sequence to reflect biological similarity, and especially to reflect antigen specificity have become of paramount importance. We review the main TCR sequence clustering methods and the different similarity measures they use, and discuss their performance and possible improvement. We aim to provide guidance for non-specialists who wish to use TCR repertoire sequencing for disease tracking, patient stratification or therapy prediction, and to provide a starting point for those aiming to develop novel techniques for TCR annotation through clustering