A5068105347- CRISPR and Genetic Engineering
- Advanced biosensing and bioanalysis techniques
- RNA and protein synthesis mechanisms
- Design Education and Practice
- Information Systems Theories and Implementation
- Evolution and Genetic Dynamics
- Manufacturing Process and Optimization
- Plant Virus Research Studies
- Innovative Human-Technology Interaction
- Biosensors and Analytical Detection
- Product Development and Customization
- SARS-CoV-2 detection and testing
- SARS-CoV-2 and COVID-19 Research
Broad Institute
2020-2024
Massachusetts Institute of Technology
2020-2022
Design of nucleic acid-based viral diagnostics typically follows heuristic rules and, to contend with variation, focuses on a genome's conserved regions. A design process could, instead, directly optimize diagnostic effectiveness using learned model sensitivity for targets and their variants. Toward that goal, we screen 19,209 diagnostic-target pairs, concentrated CRISPR-based diagnostics, train deep neural network accurately predict readout. We join this combinatorial optimization maximize...
Abstract The COVID-19 pandemic, and the recent rise widespread transmission of SARS-CoV-2 Variants Concern (VOCs), have demonstrated need for ubiquitous nucleic acid testing outside centralized clinical laboratories. Here, we develop SHINEv2, a Cas13-based diagnostic that combines quick ambient temperature sample processing lyophilized reagents to greatly simplify test procedure assay distribution. We benchmarked SHINEv2 detection against state-of-the-art antigen-capture tests using 96...
Abstract Generating maximally-fit biological sequences has the potential to transform CRISPR guide RNA design as it other areas of biomedicine. Here, we introduce model-directed exploration algorithms (MEAs) for designing maximally-fit, artificial CRISPR-Cas13a guides—with multiple mismatches any natural sequence—that are tailored desired properties around nucleic acid diagnostics. We find that MEA-designed guides offer more sensitive detection diverse pathogens and discrimination pathogen...
Abstract Diagnostics, particularly for rapidly evolving viruses, stand to benefit from a principled, measurement-driven design that harnesses machine learning and vast genomic data—yet the capability such has not been previously built. Here, we develop extensively validate an approach designing viral diagnostics applies learned model within combinatorial optimization framework. Concentrating on CRISPR-based diagnostics, screen library of 19,209 diagnostic–target pairs train deep neural...
Abstract Engineers design for an inherently uncertain world. In the early stages of processes, they commonly account such uncertainty either by manually choosing a specific worst-case and multiplying parameters with safety factors or using Monte Carlo simulations to estimate probabilistic boundaries in which their is feasible. The this first practice are determined industry organizational standards, providing limited uncertainty; second time intensive, requiring development separate testing...
When you use a computer it also uses you, and in that relationship forms new entity of melded agencies, "centaur" inseparably human nonhuman. Networks interaction an organization similarly form "organizational centaurs", melding humans, technologies, organizations into inseparable sociomateriality. By developing convex optimization toolkit for conceptual engineering we sought to shape these centaurs. How do go from high-level concept ("let's make airplane") "design", process what blurred...
Abstract Engineers design for an inherently uncertain world. In the early stages of processes, they commonly account such uncertainty either by manually choosing a specific worst-case and multiplying parameters with safety factors or using Monte Carlo simulations to estimate probabilistic boundaries in which their is feasible. The this first practice are determined industry organizational standards, providing limited uncertainty; second time intensive, requiring development separate testing...