Abstract
Ensuring the safety and suitability of proteins considered for food and biotechnology applications is an important challenge. Computational approaches can facilitate the prioritisation of candidate proteins for further investigation, particularly given the rapid growth of genomic and metagenomic sequence datasets. In this study, we developed computational models to distinguish edible plant tissue-associated (EPTA) proteins from non-EPTA proteins. The positive class comprised 939 proteins with experimentally validated evidence of expression in plant tissues commonly consumed by humans, hereafter referred to as EPTA proteins. The negative class comprised 939 proteins annotated in UniProt as toxic, allergenic, or antinutritional, hereafter referred to as non-EPTA proteins. Models were evaluated using five-fold cross-validation with a cluster-based partitioning strategy, ensuring that no protein in the validation set shared more than 40% sequence identity with proteins in the corresponding training set. First, composition-based sequence features were evaluated to establish a baseline for EPTA or non-EPTA classification, with the Extra Trees (ET) classifier achieving a validation AUROC of 0.848. To incorporate evolutionary information beyond amino acid composition, PSSM profiles were subsequently evaluated, yielding an AUROC of 0.842 with an SVM classifier. Finally, to capture richer sequence patterns and contextual information using protein language modelling, we evaluated ESM2-based models. The fine-tuned ESM2-T33 model achieved the highest validation AUROC of 0.925 and was selected as the final predictive model. The resulting approach was implemented as the EdiProPred web server (https://webs.iiitd.edu.in/raghava/edipropred/) and standalone software for computational classification of plant proteins. The EdiProPred framework provides a useful computational tool for prioritising candidate plant proteins and facilitating the exploration of novel protein resources for food and biotechnology applications.