LENS: Landscape of Effective Neoantigens Software.

Motivation: Elimination of cancer cells by T cells is a critical mechanism of anti-tumor immunity and cancer immunotherapy response. T cells recognize cancer cells by engagement of T cell receptors with peptide epitopes presented by major histocompatibility complex molecules on the cancer cell surface. Peptide epitopes can be derived from antigen proteins coded for by multiple genomic sources.

Associations of minor histocompatibility antigens with outcomes following allogeneic hematopoietic cell transplantation.

The role of minor histocompatibility antigens (mHAs) in mediating graft versus leukemia and graft versus host disease (GvHD) following allogeneic hematopoietic cell transplantation (alloHCT) is recognized but not well-characterized. By implementing improved methods for mHA prediction in two large patient cohorts, this study aimed to comprehensively explore the role of mHAs in alloHCT by analyzing whether (1) the number of predicted mHAs, or (2) individual mHAs are associated with clinical outcomes. The study population consisted of 2249 donor-recipient pairs treated for acute myeloid leukemia and myelodysplastic syndrome with alloHCT.

Evaluation of tumor antigen-specific antibody responses in patients with metastatic triple negative breast cancer treated with cyclophosphamide and pembrolizumab.

The role of B cells in antitumor immunity is becoming increasingly appreciated, as B cell populations have been associated with response to immune checkpoint blockade (ICB) in patients with breast cancer and murine models of breast cancer. Deeper understanding of antibody responses to tumor antigens is needed to clarify the function of B cells in determining response to immunotherapy. We evaluated tumor antigen-specific antibody responses in patients with metastatic triple negative breast cancer treated with pembrolizumab following low-dose cyclophosphamide therapy using computational linear epitope prediction and custom peptide microarrays.

Shared graft-versus-leukemia minor histocompatibility antigens in DISCOVeRY-BMT.

T-cell responses to minor histocompatibility antigens (mHAs) mediate graft-versus-leukemia (GVL) effects and graft-versus-host disease (GVHD) in allogeneic hematopoietic cell transplantation. Therapies that boost T-cell responses improve allogeneic hematopoietic cell transplant (alloHCT) efficacy but are limited by concurrent increases in the incidence and severity of GVHD. mHAs with expression restricted to hematopoietic tissue (GVL mHAs) are attractive targets for driving GVL without causing GVHD.

Comprehensive Analysis of the Immunogenomics of Triple-Negative Breast Cancer Brain Metastases From LCCC1419.

Background: Triple negative breast cancer (TNBC) is an aggressive variant of breast cancer that lacks the expression of estrogen and progesterone receptors (ER and PR) and HER2. Nearly 50% of patients with advanced TNBC will develop brain metastases (BrM), commonly with progressive extracranial disease. Immunotherapy has shown promise in the treatment of advanced TNBC; however, the immune contexture of BrM remains largely unknown.

NeoSplice: a bioinformatics method for prediction of splice variant neoantigens.

Motivation: Splice variant neoantigens are a potential source of tumor-specific antigen (TSA) that are shared between patients in a variety of cancers, including acute myeloid leukemia. Current tools for genomic prediction of splice variant neoantigens demonstrate promise. However, many tools have not been well validated with simulated and/or wet lab approaches, with no studies published that have presented a targeted immunopeptidome mass spectrometry approach designed specifically for identification of predicted splice variant neoantigens.

Landscape and selection of vaccine epitopes in SARS-CoV-2.

Background: Early in the pandemic, we designed a SARS-CoV-2 peptide vaccine containing epitope regions optimized for concurrent B cell, CD4 T cell, and CD8 T cell stimulation. The rationale for this design was to drive both humoral and cellular immunity with high specificity while avoiding undesired effects such as antibody-dependent enhancement (ADE).

Methods: We explored the set of computationally predicted SARS-CoV-2 HLA-I and HLA-II ligands, examining protein source, concurrent human/murine coverage, and population coverage.

Landscape and Selection of Vaccine Epitopes in SARS-CoV-2.

There is an urgent need for a vaccine with efficacy against SARS-CoV-2. We hypothesize that peptide vaccines containing epitope regions optimized for concurrent B cell, CD4 T cell, and CD8 T cell stimulation would drive both humoral and cellular immunity with high specificity, potentially avoiding undesired effects such as antibody-dependent enhancement (ADE). Additionally, such vaccines can be rapidly manufactured in a distributed manner.

Recent progress and open questions in Drosophila dosage compensation.

Sexual dimorphism is observed in many traits across diverse taxa, and often it is quite extreme. Within a species, individuals of opposing sex can appear strikingly different, reflecting differences at the molecular level that may be similarly striking. Among the most extreme cases of such molecular sexual dimorphism is the quantity of sex chromosomes that each sex possesses.

No evidence for a global male-specific lethal complex-mediated dosage compensation contribution to the demasculinization of the Drosophila melanogaster X chromosome.

In Drosophila melanogaster males, the expression of X-linked genes is regulated by mechanisms that operate on a chromosomal scale. One such mechanism, male-specific lethal complex-dependent X-linked dosage compensation, is thought to broadly enhance the expression of male X-linked genes through two-fold transcriptional upregulation. The evolutionary consequences of this form of dosage compensation are not well understood, particularly with regard to genes more highly expressed in males.

Conservation and sex-specific splicing of the transformer gene in the calliphorids Cochliomyia hominivorax, Cochliomyia macellaria and Lucilia sericata.

Transformer (TRA) promotes female development in several dipteran species including the Australian sheep blowfly Lucilia cuprina, the Mediterranean fruit fly, housefly and Drosophila melanogaster. tra transcripts are sex-specifically spliced such that only the female form encodes full length functional protein. The presence of six predicted TRA/TRA2 binding sites in the sex-specific female intron of the L.