Sai T. Reddy
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View article: SCOPE-MRI: Bankart lesion detection as a case study in data curation and deep learning for challenging diagnoses
SCOPE-MRI: Bankart lesion detection as a case study in data curation and deep learning for challenging diagnoses Open
View article: A yeast mating-based platform enables the generation and screening of ultra large antibody libraries
A yeast mating-based platform enables the generation and screening of ultra large antibody libraries Open
Yeast display is a powerful platform for antibody engineering, offering eukaryotic protein folding and compatibility with fluorescence-activated sorting (FACS). However, conventional yeast display faces limitations in terms of library size…
View article: High-throughput cell-free profiling of SARS-CoV-2 RBD variants enables rapid and quantitative in vitro affinity landscape mapping
High-throughput cell-free profiling of SARS-CoV-2 RBD variants enables rapid and quantitative in vitro affinity landscape mapping Open
SARS-CoV-2 variants continue to threaten public health, necessitating the study of cumulative and epistatic effects of receptor-binding domain (RBD) mutations on antibody evasion. We present a high-throughput platform combining cell-free p…
View article: Synthetic coevolution reveals adaptive mutational trajectories of neutralizing antibodies and SARS-CoV-2
Synthetic coevolution reveals adaptive mutational trajectories of neutralizing antibodies and SARS-CoV-2 Open
The COVID-19 pandemic showcased a coevolutionary race between the human immune system and SARS-CoV-2, during which the immune system generated neutralizing antibodies targeting the SARS-CoV-2 spike protein's receptor-binding domain (RBD), …
View article: Predicting TCR antigen specificity at proteome-scale with synthetic immune cells and machine learning
Predicting TCR antigen specificity at proteome-scale with synthetic immune cells and machine learning Open
TCR specificity to peptide-HLA antigens is central to immunology, impacting responses in infection, autoimmunity and cancer. Achieving precise recognition while avoiding off-target reactivity is critical for effective immunity and safe the…
View article: Screening of a pooled library of chimeric antigen receptor T cells based on secretory function
Screening of a pooled library of chimeric antigen receptor T cells based on secretory function Open
Chimeric antigen receptor (CAR) T cell therapies have shown promise in treating hematologic malignancies, but challenges remain due to immune suppression, antigen heterogeneity, and insufficient functional screening platforms. Here, we pre…
View article: Dissecting serum polyclonal antibody escape to SARS-CoV-2 variants by deep mutational learning
Dissecting serum polyclonal antibody escape to SARS-CoV-2 variants by deep mutational learning Open
The rapid emergence of SARS-CoV-2 variants harboring multiple receptor-binding domain (RBD) mutations continues to challenge the efficacy of vaccines and antibody therapeutics. While deep mutational scanning (DMS) has been instrumental in …
View article: Deep mutational learning for the selection of therapeutic antibodies resistant to the evolution of Omicron variants of SARS-CoV-2
Deep mutational learning for the selection of therapeutic antibodies resistant to the evolution of Omicron variants of SARS-CoV-2 Open
Most antibodies for treating COVID-19 rely on binding the receptor-binding domain (RBD) of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). However, Omicron and its sub-lineages, as well as other heavily mutated variants, have…
View article: Dissecting the role of CAR signaling architectures on T cell activation and persistence using pooled screens and single-cell sequencing
Dissecting the role of CAR signaling architectures on T cell activation and persistence using pooled screens and single-cell sequencing Open
Chimeric antigen receptor (CAR) T cells offer a promising cancer treatment, yet challenges such as limited T cell persistence hinder efficacy. Given its critical role in modulating T cell responses, it is crucial to understand how the CAR …
View article: High-Throughput Antibody Neutralization Screening in Massively Parallel Droplet Arrays
High-Throughput Antibody Neutralization Screening in Massively Parallel Droplet Arrays Open
Neutralizing antibodies provide rapid immune defense against infectious diseases, but are difficult to discover at scale because neutralization assays require live reporter cells and soluble monoclonal antibodies. Here we report Droplet Re…
View article: PLMFit : Benchmarking Transfer Learning with Protein Language Models for Protein Engineering
PLMFit : Benchmarking Transfer Learning with Protein Language Models for Protein Engineering Open
Protein language models (PLMs) have emerged as a useful resource for protein engineering applications. Transfer learning (TL) leverages pre-trained parameters to extract features to train machine learning models or adjust the weights of PL…
View article: Antibody affinity engineering using antibody repertoire data and machine learning
Antibody affinity engineering using antibody repertoire data and machine learning Open
Advanced antibody discovery and engineering workflows take advantage of the combination of high-throughput screening, deep sequencing and machine learning (ML). Most high-throughput methods, however, lack the resolution to provide absolute…
View article: Toward Non-Invasive Diagnosis of Bankart Lesions with Deep Learning
Toward Non-Invasive Diagnosis of Bankart Lesions with Deep Learning Open
Bankart lesions, or anterior-inferior glenoid labral tears, are diagnostically challenging on standard MRIs due to their subtle imaging features-often necessitating invasive MRI arthrograms (MRAs). This study develops deep learning (DL) mo…
View article: Predicting adaptive immune receptor specificities by machine learning is a data generation problem
Predicting adaptive immune receptor specificities by machine learning is a data generation problem Open
Determining the specificity of adaptive immune receptors-B cell receptors (BCRs), their secreted form antibodies, and T cell receptors (TCRs)-is critical for understanding immune responses and advancing immunotherapy and drug discovery. Im…
View article: Evaluating predictive patterns of antigen-specific B cells by single-cell transcriptome and antibody repertoire sequencing
Evaluating predictive patterns of antigen-specific B cells by single-cell transcriptome and antibody repertoire sequencing Open
The field of antibody discovery typically involves extensive experimental screening of B cells from immunized animals. Machine learning (ML)-guided prediction of antigen-specific B cells could accelerate this process but requires sufficien…
View article: Modeling CAR Response at the Single-Cell Level Using Conditional Optimal Transport
Modeling CAR Response at the Single-Cell Level Using Conditional Optimal Transport Open
Chimeric Antigen Receptor (CAR) T cell therapy is a promising area of cancer immunotherapy. However, many challenges such as loss of persistence, T cell exhaustion, and therapy associated toxicities hamper further advancement of CAR T cell…
View article: The physiological landscape and specificity of antibody repertoires are consolidated by multiple immunizations
The physiological landscape and specificity of antibody repertoires are consolidated by multiple immunizations Open
Diverse antibody repertoires spanning multiple lymphoid organs (i.e., bone marrow, spleen, lymph nodes) form the foundation of protective humoral immunity. Changes in their composition across lymphoid organs are a consequence of B-cell sel…
View article: Engineering next-generation chimeric antigen receptor-T cells: recent breakthroughs and remaining challenges in design and screening of novel chimeric antigen receptor variants
Engineering next-generation chimeric antigen receptor-T cells: recent breakthroughs and remaining challenges in design and screening of novel chimeric antigen receptor variants Open
Chimeric antigen receptor (CAR) T cells are a powerful treatment against hematologic cancers. The functional phenotype of a CAR-T cell is influenced by the domains that comprise the synthetic receptor. Typically, the potency of therapeutic…
View article: Engineered allogeneic T cells decoupling T-cell-receptor and CD3 signalling enhance the antitumour activity of bispecific antibodies
Engineered allogeneic T cells decoupling T-cell-receptor and CD3 signalling enhance the antitumour activity of bispecific antibodies Open
View article: Author response: The physiological landscape and specificity of antibody repertoires are consolidated by multiple immunizations
Author response: The physiological landscape and specificity of antibody repertoires are consolidated by multiple immunizations Open
View article: Drug-controlled CAR-T cells through the regulation of cell-cell interactions
Drug-controlled CAR-T cells through the regulation of cell-cell interactions Open
CAR T-cell therapy is constrained by on-target, off-tumor toxicities as well as cellular exhaustion due to chronic antigen exposure. CARs comprising small-molecule controlled switches can enhance both safety and therapeutic efficacy but ar…
View article: TCR clustering by contrastive learning on antigen specificity
TCR clustering by contrastive learning on antigen specificity Open
Effective clustering of T-cell receptor (TCR) sequences could be used to predict their antigen-specificities. TCRs with highly dissimilar sequences can bind to the same antigen, thus making their clustering into a common antigen group a ce…
View article: TCR clustering by contrastive learning on antigen specificity
TCR clustering by contrastive learning on antigen specificity Open
Effective clustering of T-cell receptor (TCR) sequences could be used to predict their antigen-specificities. TCRs with highly dissimilar sequences can bind to the same antigen, thus making their clustering into a common antigen group a ce…
View article: Synthetic coevolution reveals adaptive mutational trajectories of neutralizing antibodies and SARS-CoV-2
Synthetic coevolution reveals adaptive mutational trajectories of neutralizing antibodies and SARS-CoV-2 Open
The Covid-19 pandemic showcases a coevolutionary race between the human immune system and SARS-CoV-2, mirroring the Red Queen hypothesis of evolutionary biology. The immune system generates neutralizing antibodies targeting the SARS-CoV-2 …
View article: Exploring Socioeconomic Disparities in Mandibular Trauma: A Retrospective Cohort Analysis of Patient Profiles and Treatment Outcomes
Exploring Socioeconomic Disparities in Mandibular Trauma: A Retrospective Cohort Analysis of Patient Profiles and Treatment Outcomes Open
Study Design Retrospective Chart Review. Objective Mandible fracture is a life-altering event, and its complications can have devastating consequences for patients. Patients are therefore well-served if providers can identify their risk fa…
View article: Dissecting the role of CAR signaling architectures on T cell activation and persistence using pooled screening and single-cell sequencing
Dissecting the role of CAR signaling architectures on T cell activation and persistence using pooled screening and single-cell sequencing Open
Chimeric antigen receptor (CAR) T cells represent a promising approach for cancer treatment, yet challenges remain such as limited efficacy due to a lack of T cell persistence. Given its critical role in promoting and modulating T cell res…
View article: Self-assembled and perfusable microvasculature-on-chip for modeling leukocyte trafficking
Self-assembled and perfusable microvasculature-on-chip for modeling leukocyte trafficking Open
We developed and characterized a biologically functional microcirculation system consisting of arterial and venous endothelial cells and pericytes. The model was employed to study leukocyte transendothelial migration in the healthy and inf…
View article: Deep learning-guided selection of antibody therapies with enhanced resistance to current and prospective SARS-CoV-2 Omicron variants
Deep learning-guided selection of antibody therapies with enhanced resistance to current and prospective SARS-CoV-2 Omicron variants Open
Most COVID-19 antibody therapies rely on binding the SARS-CoV-2 receptor binding domain (RBD). However, heavily mutated variants such as Omicron and its sublineages, which are characterized by an ever increasing number of mutations in the …
View article: Multimodal single-cell profiling of T cell specificity and reactivity in lung cancer
Multimodal single-cell profiling of T cell specificity and reactivity in lung cancer Open
SUMMARY Adoptive transfer of autologous tumor-infiltrating lymphocyte T cells (TILs) offers one of the most promising approaches for cancer immunotherapy. However, high variability in patient responses highlight the need for an enhanced un…
View article: ePlatypus: an ecosystem for computational analysis of immunogenomics data
ePlatypus: an ecosystem for computational analysis of immunogenomics data Open
Motivation The maturation of systems immunology methodologies requires novel and transparent computational frameworks capable of integrating diverse data modalities in a reproducible manner. Results Here, we present the ePlatypus computati…