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The formation of complex traits is the consequence of genotype and activities at multiple molecular levels. However, connecting genotypes and these activities to complex traits remains challenging. Here, we investigate whether integrating genomic, transcriptomic, and methylomic data can improve pre- diction for six Arabidopsis traits. We find that transcriptome- and methylome- based models have performances comparable to those of genome-based models. However, models built for flowering time using different omics data identify different benchmark genes. Nine additional genes identified as important for flowering time from our models are experimentally validated as regulating flowering. Gene contributions to flowering time prediction are accession-dependent and distinct genes contribute to trait prediction in dif- ferent genotypes. Models integrating multi-omics data perform best and reveal known and additional gene interactions, extending knowledge about existing regulatory networks underlying flowering time determination. These results demonstrate the feasibility of revealing molecular mechanisms underlying complex traits through multi-omics data integration. 

Abstract Natural language processing (NLP) techniques can enhance our ability to interpret plant science literature. Many state-of-the-art algorithms for NLP tasks require high-quality labelled data in the target domain, in which entities like genes and proteins, as well as the relationships between entities, are labelled according to a set of annotation guidelines. While there exist such datasets for other domains, these resources need development in the plant sciences. Here, we present the Plant ScIenCe KnowLedgE Graph (PICKLE) corpus, a collection of 250 plant science abstracts annotated with entities and relations, along with its annotation guidelines. The annotation guidelines were refined by iterative rounds of overlapping annotations, in which inter-annotator agreement was leveraged to improve the guidelines. To demonstrate PICKLE’s utility, we evaluated the performance of pretrained models from other domains and trained a new, PICKLE-based model for entity and relation extraction (RE). The PICKLE-trained models exhibit the second-highest in-domain entity performance of all models evaluated, as well as a RE performance that is on par with other models. Additionally, we found that computer science-domain models outperformed models trained on a biomedical corpus (GENIA) in entity extraction, which was unexpected given the intuition that biomedical literature is more similar to PICKLE than computer science. Upon further exploration, we established that the inclusion of new types on which the models were not trained substantially impacts performance. The PICKLE corpus is, therefore, an important contribution to training resources for entity and RE in the plant sciences. 

Abstract Genetic redundancy refers to a situation where an individual with a loss-of-function mutation in one gene (single mutant) does not show an apparent phenotype until one or more paralogs are also knocked out (double/higher-order mutant). Previous studies have identified some characteristics common among redundant gene pairs, but a predictive model of genetic redundancy incorporating a wide variety of features derived from accumulating omics and mutant phenotype data is yet to be established. In addition, the relative importance of these features for genetic redundancy remains largely unclear. Here, we establish machine learning models for predicting whether a gene pair is likely redundant or not in the model plant Arabidopsis thaliana based on six feature categories: functional annotations, evolutionary conservation including duplication patterns and mechanisms, epigenetic marks, protein properties including post-translational modifications, gene expression, and gene network properties. The definition of redundancy, data transformations, feature subsets, and machine learning algorithms used significantly affected model performance based on hold-out, testing phenotype data. Among the most important features in predicting gene pairs as redundant were having a paralog(s) from recent duplication events, annotation as a transcription factor, downregulation during stress conditions, and having similar expression patterns under stress conditions. We also explored the potential reasons underlying mispredictions and limitations of our studies. This genetic redundancy model sheds light on characteristics that may contribute to long-term maintenance of paralogs, and will ultimately allow for more targeted generation of functionally informative double mutants, advancing functional genomic studies.