Machine Learning and Artificial Intelligence (AI) more broadly have great immediate and future potential for transforming almost all aspects of medicine. However, in many applications, even outside medicine, a lack of transparency in AI applications has become increasingly problematic. This is particularly pronounced where users need to interpret the output of AI systems. Explainable AI (XAI) provides a rationale that allows users to understand why a system has produced a given output. The output can then be interpreted within a given context. One area that is in great need of XAI is that of Clinical Decision Support Systems (CDSSs). These systems support medical practitioners in their clinic decision-making and in the absence of explainability may lead to issues of under or over-reliance. Providing explanations for how recommendations are arrived at will allow practitioners to make more nuanced, and in some cases, life-saving decisions. The need for XAI in CDSS, and the medical field in general, is amplified by the need for ethical and fair decision-making and the fact that AI trained with historical data can be a reinforcement agent of historical actions and biases that should be uncovered. We performed a systematic literature review of work to-date in the application of XAI in CDSS. Tabular data processing XAI-enabled systems are the most common, while XAI-enabled CDSS for text analysis are the least common in literature. There is more interest in developers for the provision of local explanations, while there was almost a balance between post-hoc and ante-hoc explanations, as well as between model-specific and model-agnostic techniques. Studies reported benefits of the use of XAI such as the fact that it could enhance decision confidence for clinicians, or generate the hypothesis about causality, which ultimately leads to increased trustworthiness and acceptability of the system and potential for its incorporation in the clinical workflow. However, we found an overall distinct lack of application of XAI in the context of CDSS and, in particular, a lack of user studies exploring the needs of clinicians. We propose some guidelines for the implementation of XAI in CDSS and explore some opportunities, challenges, and future research needs.

The conventional wisdom is that certain classes of bioactive peptides have specific structural features that endow their particular functions. Accordingly, predictions of bioactivity have focused on particular subgroups, such as antimicrobial peptides. We hypothesized that bioactive peptides may share more general features, and assessed this by contrasting the predictive power of existing antimicrobial predictors as well as a novel general predictor, PeptideRanker, across different classes of peptides. We observed that existing antimicrobial predictors had reasonable predictive power to identify peptides of certain other classes i.e. toxin and venom peptides. We trained two general predictors of peptide bioactivity, one focused on short peptides (4–20 amino acids) and one focused on long peptides ( amino acids). These general predictors had performance that was typically as good as, or better than, that of specific predictors. We noted some striking differences in the features of short peptide and long peptide predictions, in particular, high scoring short peptides favour phenylalanine. This is consistent with the hypothesis that short and long peptides have different functional constraints, perhaps reflecting the difficulty for typical short peptides in supporting independent tertiary structure. We conclude that there are general shared features of bioactive peptides across different functional classes, indicating that computational prediction may accelerate the discovery of novel bioactive peptides and aid in the improved design of existing peptides, across many functional classes. An implementation of the predictive method, PeptideRanker, may be used to identify among a set of peptides those that may be more likely to be bioactive.

Summary: Cell penetrating peptides (CPPs) are attracting much attention as a means of overcoming the inherently poor cellular uptake of various bioactive molecules. Here, we introduce CPPpred, a web server for the prediction of CPPs using a N-to-1 neural network. The server takes one or more peptide sequences, between 5 and 30 amino acids in length, as input and returns a prediction of how likely each peptide is to be cell penetrating. CPPpred was developed with redundancy reduced training and test sets, offering an advantage over the only other currently available CPP prediction method. Availability and Implementation: CPPpred is freely available to non-commercial users at http://bioware.ucd.ie/cpppred. Contact:Denis.Shields@ucd.ie Supplementary Information: Supplementary data are available at Bioinformatics online.

Gestational Diabetes Mellitus (GDM), a common pregnancy complication associated with many maternal and neonatal consequences, is increased in mothers with overweight and obesity. Interventions initiated early in pregnancy can reduce the rate of GDM in these women, however, untargeted interventions can be costly and time-consuming. We have developed an explainable machine learning-based clinical decision support system (CDSS) to identify at-risk women in need of targeted pregnancy intervention. Maternal characteristics and blood biomarkers at baseline from the PEARS study were used. After appropriate data preparation, synthetic minority oversampling technique and feature selection, five machine learning algorithms were applied with five-fold cross-validated grid search optimising the balanced accuracy. Our models were explained with Shapley additive explanations to increase the trustworthiness and acceptability of the system. We developed multiple models for different use cases: theoretical (AUC-PR 0.485, AUC-ROC 0.792), GDM screening during a normal antenatal visit (AUC-PR 0.208, AUC-ROC 0.659), and remote GDM risk assessment (AUC-PR 0.199, AUC-ROC 0.656). Our models have been implemented as a web server that is publicly available for academic use. Our explainable CDSS demonstrates the potential to assist clinicians in screening at risk patients who may benefit from early pregnancy GDM prevention strategies.