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Artificial intelligence predicts the immunogenic landscape of SARS-CoV-2 leading to universal blueprints for vaccine designs.

ABSTRACT: The global population is at present suffering from a pandemic of Coronavirus disease 2019 (COVID-19), caused by the novel coronavirus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The goal of this study was to use artificial intelligence (AI) to predict blueprints for designing universal vaccines against SARS-CoV-2, that contain a sufficiently broad repertoire of T-cell epitopes capable of providing coverage and protection across the global population. To help achieve these aims, we profiled the entire SARS-CoV-2 proteome across the most frequent 100 HLA-A, HLA-B and HLA-DR alleles in the human population, using host-infected cell surface antigen presentation and immunogenicity predictors from the NEC Immune Profiler suite of tools, and generated comprehensive epitope maps. We then used these epitope maps as input for a Monte Carlo simulation designed to identify statistically significant "epitope hotspot" regions in the virus that are most likely to be immunogenic across a broad spectrum of HLA types. We then removed epitope hotspots that shared significant homology with proteins in the human proteome to reduce the chance of inducing off-target autoimmune responses. We also analyzed the antigen presentation and immunogenic landscape of all the nonsynonymous mutations across 3,400 different sequences of the virus, to identify a trend whereby SARS-COV-2 mutations are predicted to have reduced potential to be presented by host-infected cells, and consequently detected by the host immune system. A sequence conservation analysis then removed epitope hotspots that occurred in less-conserved regions of the viral proteome. Finally, we used a database of the HLA haplotypes of approximately 22,000 individuals to develop a "digital twin" type simulation to model how effective different combinations of hotspots would work in a diverse human population; the approach identified an optimal constellation of epitope hotspots that could provide maximum coverage in the global population. By combining the antigen presentation to the infected-host cell surface and immunogenicity predictions of the NEC Immune Profiler with a robust Monte Carlo and digital twin simulation, we have profiled the entire SARS-CoV-2 proteome and identified a subset of epitope hotspots that could be harnessed in a vaccine formulation to provide a broad coverage across the global population.

SUBMITTER: Malone B

PROVIDER: S-EPMC7758335 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Artificial intelligence predicts the immunogenic landscape of SARS-CoV-2 leading to universal blueprints for vaccine designs.

Malone Brandon B Simovski Boris B Moliné Clément C Cheng Jun J Gheorghe Marius M Fontenelle Hugues H Vardaxis Ioannis I Tennøe Simen S Malmberg Jenny-Ann JA Stratford Richard R Clancy Trevor T

Scientific reports 20201223 1

The global population is at present suffering from a pandemic of Coronavirus disease 2019 (COVID-19), caused by the novel coronavirus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The goal of this study was to use artificial intelligence (AI) to predict blueprints for designing universal vaccines against SARS-CoV-2, that contain a sufficiently broad repertoire of T-cell epitopes capable of providing coverage and protection across the global population. To help achieve these aims, ...[more]

PMID: 33361777

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Project description:ImportanceThe progression of artificial intelligence (AI) text-to-image generators raises concerns of perpetuating societal biases, including profession-based stereotypes.ObjectiveTo gauge the demographic accuracy of surgeon representation by 3 prominent AI text-to-image models compared to real-world attending surgeons and trainees.Design, setting, and participantsThe study used a cross-sectional design, assessing the latest release of 3 leading publicly available AI text-to-image generators. Seven independent reviewers categorized AI-produced images. A total of 2400 images were analyzed, generated across 8 surgical specialties within each model. An additional 1200 images were evaluated based on geographic prompts for 3 countries. The study was conducted in May 2023. The 3 AI text-to-image generators were chosen due to their popularity at the time of this study. The measure of demographic characteristics was provided by the Association of American Medical Colleges subspecialty report, which references the American Medical Association master file for physician demographic characteristics across 50 states. Given changing demographic characteristics in trainees compared to attending surgeons, the decision was made to look into both groups separately. Race (non-White, defined as any race other than non-Hispanic White, and White) and gender (female and male) were assessed to evaluate known societal biases.ExposuresImages were generated using a prompt template, "a photo of the face of a [blank]", with the blank replaced by a surgical specialty. Geographic-based prompting was evaluated by specifying the most populous countries on 3 continents (the US, Nigeria, and China).Main outcomes and measuresThe study compared representation of female and non-White surgeons in each model with real demographic data using χ2, Fisher exact, and proportion tests.ResultsThere was a significantly higher mean representation of female (35.8% vs 14.7%; P < .001) and non-White (37.4% vs 22.8%; P < .001) surgeons among trainees than attending surgeons. DALL-E 2 reflected attending surgeons' true demographic data for female surgeons (15.9% vs 14.7%; P = .39) and non-White surgeons (22.6% vs 22.8%; P = .92) but underestimated trainees' representation for both female (15.9% vs 35.8%; P < .001) and non-White (22.6% vs 37.4%; P < .001) surgeons. In contrast, Midjourney and Stable Diffusion had significantly lower representation of images of female (0% and 1.8%, respectively; P < .001) and non-White (0.5% and 0.6%, respectively; P < .001) surgeons than DALL-E 2 or true demographic data. Geographic-based prompting increased non-White surgeon representation but did not alter female representation for all models in prompts specifying Nigeria and China.Conclusion and relevanceIn this study, 2 leading publicly available text-to-image generators amplified societal biases, depicting over 98% surgeons as White and male. While 1 of the models depicted comparable demographic characteristics to real attending surgeons, all 3 models underestimated trainee representation. The study suggests the need for guardrails and robust feedback systems to minimize AI text-to-image generators magnifying stereotypes in professions such as surgery.

Project description:PurposeTo develop and internally validate a machine-learning algorithm to reliably predict cost after anterior cruciate ligament reconstruction (ACLR).MethodsA retrospective review of the New York State Ambulatory Surgery and Services database was performed to identify patients who underwent elective ACLR from 2015 to 2016. Features included in initial models consisted of patient characteristics (age, sex, insurance status, income, medical comorbidities as classified by the Clinical Classifications Software diagnosis code) as well as intraoperative variables (type of anesthesia and procedure-specific factors). Models were generated to predict total charges using 4 algorithms: random forest, extreme gradient boost, elastic net penalized regression, and support vector machines with radial kernels. Training was performed with 10-fold cross-validation followed by internal validation via 0.632 bootstrapping. Model discriminative performance was assessed by area under the receiver operating characteristic curve, calibration, and the Brier score. Decision curve analysis was performed to demonstrate the net benefit of using the final model in practice.ResultsIn total, 7,311 patients undergoing ambulatory ACLR were included. The random forest model demonstrated the best performance assessed via internal validation (area under the curve = 0.85), calibration, and the Brier score (0.208). Cost incurred was influenced by anesthesia type, operating room time, and number of chronic comorbidities. Decision curve analysis revealed a net benefit for use of the random forest model and the model was integrated into a web-based open-access application.ConclusionsThe random forest model predicted cost after ambulatory ACLR using a large, statewide database with good performance. The top variables found to predict increased charges were general anesthesia, operating room time, meniscal repair, self-pay insurance, patient neighborhood characteristics, and number of chronic conditions.Level of evidenceIII, retrospective cohort study.

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Artificial intelligence predicts the immunogenic landscape of SARS-CoV-2 leading to universal blueprints for vaccine designs.

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Artificial intelligence predicts the immunogenic landscape of SARS-CoV-2 leading to universal blueprints for vaccine designs.

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