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

Single cell dissection of plasma cell heterogeneity in symptomatic and asymptomatic myeloma

Multiple myeloma, a plasma cell malignancy, is the second most common blood cancer. Despite extensive research, disease heterogeneity is poorly characterized, hampering efforts for early diagnosis and improved treatments. Here, we apply single cell RNA sequencing to study the heterogeneity of 40 individuals along the multiple myeloma progression spectrum, including 11 healthy controls, demonstrating high interindividual variability that can be explained by expression of known multiple myeloma drivers and additional putative factors. We identify extensive subclonal structures for 10 of 29 individuals with multiple myeloma. In asymptomatic individuals with early disease and in those with minimal residual disease post-treatment, we detect rare tumor plasma cells with molecular characteristics similar to those of active myeloma, with possible implications for personalized therapies. Single cell analysis of rare circulating tumor cells allows for accurate liquid biopsy and detection of malignant plasma cells, which reflect bone marrow disease. Our work establishes single cell RNA sequencing for dissecting blood malignancies and devising detailed molecular characterization of tumor cells in symptomatic and asymptomatic patients

Exploring Play and Playfulness in the Everyday Lives of Older Women

There is an emerging body of literature about older women and play, often focused on social groupings (e.g., Red Hats Society, Raging Grannies). This study aimed to contribute to this body of literature by exploring the meaning, experience, and place of play and playfulness in the day-to-day lives of older women. Interpreting older women’s play as a phenomenologist informed by the feminist gerontology literature, I explored, described, and interpreted play using the voices, words, lived experiences, and artful reflections of four focus groups comprised of nineteen women between the ages of 63 to 95 years. Play emerged to be a wonderful, complex, and paradoxical phenomenon for older women that interconnected in three ways: as a doing, a feeling, and a being. Within and across the women, play was characterized by these paradoxes: time flies by and time slows down, productive and unproductive, social and solitary, and serious and silly. Play was infused into the everyday lives of these older women. Arts-based methods served to invigorate and engage the women and me, and transformed the research environment into a comfortable, open space to play and be playful, and to share, gather, and build knowledge. Thus this research contributes to the growing body of literature about the lives and experiences of older women, from their perspective, adds insight into older women’s play, and grows our knowledge about collecting data through arts-based methods with older women