The present disclosure describes methods for determining the functional consequences of mutations. The methods include the use of machine learning to identify and quantify features of all atom molecular dynamics simulations to obtain the disruptive severity of genetic variants on molecular function.

A system and method for feedback-driven automated drug discovery which combines machine learning algorithms with automated research facilities and equipment to make the process of drug discovery more data driven and less reliant on intuitive decision-making by experts. In an embodiment, the system comprises automated research equipment configured to perform automated assays of chemical compounds, a data platform comprising drug databases and an analysis engine, a bioactivity and de novo modules operating on the data platform, and a retrosynthesis system operating on the drug discovery platform, all configured in a feedback loop that drives drug discovery by using the outcome of assays performed on the automated research equipment to feed the bioactivity module and retrosynthesis systems, which identify new molecules for testing by the automated research equipment.

A system and method for feedback-driven automated drug discovery which combines machine learning algorithms with automated research facilities and equipment to make the process of drug discovery more data driven and less reliant on intuitive decision-making by experts. In an embodiment, the system comprises automated research equipment configured to perform automated assays of chemical compounds, a data platform comprising drug databases and an analysis engine, a bioactivity and de novo modules operating on the data platform, and a retrosynthesis system operating on the drug discovery platform, all configured in a feedback loop that drives drug discovery by using the outcome of assays performed on the automated research equipment to feed the bioactivity module and retrosynthesis systems, which identify new molecules for testing by the automated research equipment.

A system and method for optimizing the latent space in generative machine learning models, and applications of the optimizations for use in the de novo generation of molecules for both ligand-based and pocket-based generation. The ligand-based optimizations comprise a tunable reward system based on a multi-property model and further define new measurable metrics: molecular novelty and uniqueness. The pocket-based optimizations comprise an initial multi-property optimization followed up by either a seed-based optimization or a relaxed-based optimization.

A system and method for optimizing the latent space in generative machine learning models, and applications of the optimizations for use in the de novo generation of molecules for both ligand-based and pocket-based generation. The ligand-based optimizations comprise a tunable reward system based on a multi-property model and further define new measurable metrics: molecular novelty and uniqueness. The pocket-based optimizations comprise an initial multi-property optimization followed up by either a seed-based optimization or a relaxed-based optimization.

An incremental author disambiguation framework may create new clusters to accommodate new data based on the existing cluster results and newly added data. The proposed system may provide frequent update of taxonomic classification, name disambiguation and many other applications because it takes less time to generate new results. In addition, the proposed methods may reduce the time needed for updating the model and help improve the performance with the limited computational resource.

An incremental author disambiguation framework may create new clusters to accommodate new data based on the existing cluster results and newly added data. The proposed system may provide frequent update of taxonomic classification, name disambiguation and many other applications because it takes less time to generate new results. In addition, the proposed methods may reduce the time needed for updating the model and help improve the performance with the limited computational resource.

The methods discussed herein can extract relevant signals from sparse data sets, for instance in cryptographic analysis, noise reduction, pattern recognition, or computational genetics. The present solution can improve technological performance of an analytical device such as through reducing server load, computation time, and data storage sizes. The present solution can identify relevant signals, such as genetic variants with a high probability of pathogenicity, in large, sparse data sets.

A process including obtaining a set of natural-language text documents that discuss a topic, the set of documents containing different states of knowledge about the topic at different times. The process includes selecting an ontology from among a plurality of ontologies that correspond to different domains of knowledge, the selection being based on the ontology corresponding to a domain of knowledge including the topic. The process includes identifying concepts discussed in the documents using the ontology and detecting changes in at least some of the concepts over time based on differences between discussion of the concepts in documents authored at different times. The process includes updating natural language instructions on the topic based on the detected changes in the concepts and storing the updated natural language instructions in memory.

Disclosed herein are system, method, and computer program product embodiments for optimizing the determination of a phenotypic impact of a molecular variant identified in molecular tests, samples, or reports of subjects by way of regularly incorporating, updating, monitoring, validating, selecting, and auditing the best-performing evidence models for the interpretation of molecular variants across a plurality of evidence classes.