Graph-pMHC: graph neural network approach to MHC class II peptide presentation and antibody immunogenicity.

Antigen presentation on MHC class II (pMHCII presentation) plays an essential role in the adaptive immune response to extracellular pathogens and cancerous cells. But it can also reduce the efficacy of large-molecule drugs by triggering an anti-drug response. Significant progress has been made in pMHCII presentation modeling due to the collection of large-scale pMHC mass spectrometry datasets (ligandomes) and advances in machine learning.

A pan-cancer organoid platform for precision medicine.

Patient-derived tumor organoids (TOs) are emerging as high-fidelity models to study cancer biology and develop novel precision medicine therapeutics. However, utilizing TOs for systems-biology-based approaches has been limited by a lack of scalable and reproducible methods to develop and profile these models. We describe a robust pan-cancer TO platform with chemically defined media optimized on cultures acquired from over 1,000 patients.

Validation of a liquid biopsy assay with molecular and clinical profiling of circulating tumor DNA.

Liquid biopsy is a valuable precision oncology tool that is increasingly used as a non-invasive approach to identify biomarkers, detect resistance mutations, monitor disease burden, and identify early recurrence. The Tempus xF liquid biopsy assay is a 105-gene, hybrid-capture, next-generation sequencing (NGS) assay that detects single-nucleotide variants, insertions/deletions, copy number variants, and chromosomal rearrangements. Here, we present extensive validation studies of the xF assay using reference standards, cell lines, and patient samples that establish high sensitivity, specificity, and accuracy in variant detection.

Integrated genomic profiling expands clinical options for patients with cancer.

Genomic analysis of paired tumor-normal samples and clinical data can be used to match patients to cancer therapies or clinical trials. We analyzed 500 patient samples across diverse tumor types using the Tempus xT platform by DNA-seq, RNA-seq and immunological biomarkers. The use of a tumor and germline dataset led to substantial improvements in mutation identification and a reduction in false-positive rates.

Clinical validation of the tempus xT next-generation targeted oncology sequencing assay.

We developed and clinically validated a hybrid capture next generation sequencing assay to detect somatic alterations and microsatellite instability in solid tumors and hematologic malignancies. This targeted oncology assay utilizes tumor-normal matched samples for highly accurate somatic alteration calling and whole transcriptome RNA sequencing for unbiased identification of gene fusion events. The assay was validated with a combination of clinical specimens and cell lines, and recorded a sensitivity of 99.

Self-Antigen-Driven Thymic B Cell Class Switching Promotes T Cell Central Tolerance.

B cells are unique antigen-presenting cells because their antigen presentation machinery is closely tied to the B cell receptor. Autoreactive thymic B cells can efficiently present cognate self-antigens to mediate CD4 T cell-negative selection. However, the nature of thymocyte-thymic B cell interaction and how this interaction affects the selection of thymic B cell repertoire and, in turn, the T cell repertoire are not well understood.

The development and function of thymic B cells.

Thymic B cells are a unique population of B lymphocytes that reside at the cortico-medullary junction of the thymus, an organ that is specialized for the development and selection of T cells. These B cells are distinct from peripheral B cells both in terms of their origin and phenotype. Multiple lines of evidence suggest that they develop within the thymus from B lineage-committed progenitors and are not recirculating peripheral B cells.

Autoreactive thymic B cells are efficient antigen-presenting cells of cognate self-antigens for T cell negative selection.

The thymus contains a population of B cells that colocalize with dendritic cells and medullary thymic epithelial cells in the thymic medulla. The development and functional significance of these cells are largely unknown. Using recombination-activating gene 2 GFP reporter mice along with parabiosis experiments, we demonstrate that the vast majority of thymic B cells develop from progenitors within the thymus.

Cloning of a hamster anti-mouse CD79B antibody sequences and identification of a new hamster immunoglobulin lambda constant IGLC gene region.

Anti-CD79 antibodies have been effective at targeting B cell lymphoma cells and depleting B cells in animal models. In order to engineer recombinant antibodies with additional effector functions in mice, we cloned and sequenced the full-length cDNAs of the heavy and light chain of a hamster anti-mouse CD79B antibody. Although hamster antibodies represent a unique source of monoclonal antibodies against mouse, rat, and human antigens, sequence information of hamster immunoglobulins (IG) is sparse.

Autoreactive T and B cells induce the development of bronchus-associated lymphoid tissue in the lung.

Rheumatoid arthritis-related interstitial lung disease (RA-ILD) is associated with significant morbidity and mortality. Studies in humans have found that the incidence of bronchus-associated lymphoid tissue (BALT) correlates with the severity of lung injury. However, the mechanisms underlying the development of BALT during systemic autoimmunity remain unknown.