The Monarch Initiative in 2024: an analytic platform integrating phenotypes, genes and diseases across species.

Bridging the gap between genetic variations, environmental determinants, and phenotypic outcomes is critical for supporting clinical diagnosis and understanding mechanisms of diseases. It requires integrating open data at a global scale. The Monarch Initiative advances these goals by developing open ontologies, semantic data models, and knowledge graphs for translational research. The Monarch App is an integrated platform combining data about genes, phenotypes, and diseases across species. Monarch's APIs enable access to carefully curated datasets and advanced analysis tools that support the understanding and diagnosis of disease for diverse applications such as variant prioritization, deep phenotyping, and patient profile-matching. We have migrated our system into a scalable, cloud-based infrastructure; simplified Monarch's data ingestion and knowledge graph integration systems; enhanced data mapping and integration standards; and developed a new user interface with novel search and graph navigation features. Furthermore, we advanced Monarch's analytic tools by developing a customized plugin for OpenAI's ChatGPT to increase the reliability of its responses about phenotypic data, allowing us to interrogate the knowledge in the Monarch graph using state-of-the-art Large Language Models. The resources of the Monarch Initiative can be found at monarchinitiative.org and its corresponding code repository at github.com/monarch-initiative/monarch-app.

Computing on Phenotypic Descriptions for Candidate Gene Discovery and Crop Improvement.

Many newly observed phenotypes are first described, then experimentally manipulated. These language-based descriptions appear in both the literature and in community datastores. To standardize phenotypic descriptions and enable simple data aggregation and analysis, controlled vocabularies and specific data architectures have been developed. Such simplified descriptions have several advantages over natural language: they can be rigorously defined for a particular context or problem, they can be assigned and interpreted programmatically, and they can be organized in a way that allows for semantic reasoning (inference of implicit facts). Because researchers generally report phenotypes in the literature using natural language, curators have been translating phenotypic descriptions into controlled vocabularies for decades to make the information computable. Unfortunately, this methodology is highly dependent on human curation, which does not scale to the scope of all publications available across all of plant biology. Simultaneously, researchers in other domains have been working to enable computation on natural language. This has resulted in new, automated methods for computing on language that are now available, with early analyses showing great promise. Natural language processing (NLP) coupled with machine learning (ML) allows for the use of unstructured language for direct analysis of phenotypic descriptions. Indeed, we have found that these automated methods can be used to create data structures that perform as well or better than those generated by human curators on tasks such as predicting gene function and biochemical pathway membership. Here, we describe current and ongoing efforts to provide tools for the plant phenomics community to explore novel predictions that can be generated using these techniques. We also describe how these methods could be used along with mobile speech-to-text tools to collect and analyze in-field spoken phenotypic descriptions for association genetics and breeding applications.

Automated Methods Enable Direct Computation on Phenotypic Descriptions for Novel Candidate Gene Prediction.

Natural language descriptions of plant phenotypes are a rich source of information for genetics and genomics research. We computationally translated descriptions of plant phenotypes into structured representations that can be analyzed to identify biologically meaningful associations. These representations include the entity-quality (EQ) formalism, which uses terms from biological ontologies to represent phenotypes in a standardized, semantically rich format, as well as numerical vector representations generated using natural language processing (NLP) methods (such as the bag-of-words approach and document embedding). We compared resulting phenotype similarity measures to those derived from manually curated data to determine the performance of each method. Computationally derived EQ and vector representations were comparably successful in recapitulating biological truth to representations created through manual EQ statement curation. Moreover, NLP methods for generating vector representations of phenotypes are scalable to large quantities of text because they require no human input. These results indicate that it is now possible to computationally and automatically produce and populate large-scale information resources that enable researchers to query phenotypic descriptions directly.