Fine-tuning Protein Language Models with Deep Mutational Scanning improves Variant Effect Prediction

Protein Language Models (PLMs) have emerged as performant and scalable tools for predicting the functional impact and clinical significance of protein-coding variants, but they still lag experimental accuracy. Here, we present a novel fine-tuning approach to improve the performance of PLMs with experimental maps of variant effects from Deep Mutational Scanning (DMS) assays using a Normalised Log-odds Ratio (NLR) head. We find consistent improvements in a held-out protein test set, and on independent DMS and clinical variant annotation benchmarks from ProteinGym and ClinVar. These findings demonstrate that DMS is a promising source of sequence diversity and supervised training data for improving the performance of PLMs for variant effect prediction.

Delving Deeper into MOOC Student Dropout Prediction

In order to obtain reliable accuracy estimates for automatic MOOC dropout predictors, it is important to train and test them in a manner consistent with how they will be used in practice. Yet most prior research on MOOC dropout prediction has measured test accuracy on the same course used for training the classifier, which can lead to overly optimistic accuracy estimates. In order to understand better how accuracy is affected by the training+testing regime, we compared the accuracy of a standard dropout prediction architecture (clickstream features + logistic regression) across 4 different training paradigms. Results suggest that (1) training and testing on the same course ("post-hoc") can overestimate accuracy by several percentage points; (2) dropout classifiers trained on proxy labels based on students' persistence are surprisingly competitive with post-hoc training (87.33% versus 90.20% AUC averaged over 8 weeks of 40 HarvardX MOOCs); and (3) classifier performance does not vary significantly with the academic discipline. Finally, we also research new dropout prediction architectures based on deep, fully-connected, feed-forward neural networks and find that (4) networks with as many as 5 hidden layers can statistically significantly increase test accuracy over that of logistic regression.