Adaptive Language-based Mental Health Assessment with Item-Response Theory

Mental health issues widely vary across individuals - the manifestations of signs and symptoms can be fairly heterogeneous. Recently, language-based depression and anxiety assessments have shown promise for capturing this heterogeneous nature by evaluating a patient's own language, but such approaches require a large sample of words per person to be accurate. In this work, we introduce adaptive language-based assessment - the task of iteratively estimating an individual's psychological score based on limited language responses to questions that the model also decides to ask. To this end, we explore two statistical learning-based approaches for measurement/scoring: classical test theory (CTT) and item response theory (IRT). We find that using adaptive testing in general can significantly reduce the number of questions required to achieve high validity (r ~ 0.7) with standardized tests, bringing down from 11 total questions down to 3 for depression and 5 for anxiety. Given the combinatorial nature of the problem, we empirically evaluate multiple strategies for both the ordering and scoring objectives, introducing two new methods: a semi-supervised item response theory based method (ALIRT), and a supervised actor-critic based model. While both of the models achieve significant improvements over random and fixed orderings, we find ALIRT to be a scalable model that achieves the highest accuracy with lower numbers of questions (e.g. achieves Pearson r ~ 0.93 after only 3 questions versus asking all 11 questions). Overall, ALIRT allows prompting a reduced number of questions without compromising accuracy or overhead computational costs

Transfer and Active Learning for Dissonance Detection: Addressing the Rare-Class Challenge

While transformer-based systems have enabled greater accuracies with fewer training examples, data acquisition obstacles still persist for rare-class tasks -- when the class label is very infrequent (e.g. < 5% of samples). Active learning has in general been proposed to alleviate such challenges, but choice of selection strategy, the criteria by which rare-class examples are chosen, has not been systematically evaluated. Further, transformers enable iterative transfer-learning approaches. We propose and investigate transfer- and active learning solutions to the rare class problem of dissonance detection through utilizing models trained on closely related tasks and the evaluation of acquisition strategies, including a proposed probability-of-rare-class (PRC) approach. We perform these experiments for a specific rare class problem: collecting language samples of cognitive dissonance from social media. We find that PRC is a simple and effective strategy to guide annotations and ultimately improve model accuracy while transfer-learning in a specific order can improve the cold-start performance of the learner but does not benefit iterations of active learning

Ligand-modulated Parallel Mechanical Unfolding Pathways of Maltose-binding Proteins

Protein folding and unfolding are complex phenomena, and it is accepted that multidomain proteins generally follow multiple pathways. Maltose-binding protein (MBP) is a large (a two-domain, 370-amino acid residue) bacterial periplasmic protein involved in maltose uptake. Despite the large size, it has been shown to exhibit an apparent two-state equilibrium unfolding in bulk experiments. Single-molecule studies can uncover rare events that are masked by averaging in bulk studies. Here, we use single-molecule force spectroscopy to study the mechanical unfolding pathways of MBP and its precursor protein (preMBP) in the presence and absence of ligands. Our results show that MBP exhibits kinetic partitioning on mechanical stretching and unfolds via two parallel pathways: one of them involves a mechanically stable intermediate (path I) whereas the other is devoid of it (path II). The apoMBP unfolds via path I in 62% of the mechanical unfolding events, and the remaining 38% follow path II. In the case of maltose-bound MBP, the protein unfolds via the intermediate in 79% of the cases, the remaining 21% via path II. Similarly, on binding to maltotriose, a ligand whose binding strength with the polyprotein is similar to that of maltose, the occurrence of the intermediate is comparable (82% via path I) with that of maltose. The precursor protein preMBP also shows a similar behavior upon mechanical unfolding. The percentages of molecules unfolding via path I are 53% in the apo form and 68% and 72% upon binding to maltose and maltotriose, respectively, for preMBP. These observations demonstrate that ligand binding can modulate the mechanical unfolding pathways of proteins by a kinetic partitioning mechanism. This could be a general mechanism in the unfolding of other large two-domain ligand-binding proteins of the bacterial periplasmic space

Ligand modulated parallel mechanical unfolding pathways of Maltose binding proteins (MBPs)

Protein folding/unfolding are complex phenomena and it is accepted that multidomain proteins generally follow multiple pathways. Maltose binding protein is a large (a two-domain 370 amino acid residue) bacterial periplasmic protein involved in maltose uptake. Despite the large size, it has been shown to exhibit an apparent two-state equilibrium unfolding in bulk experiments. Single-molecule studies can uncover rare events that are masked by averaging in bulk studies. Here, we use single-molecule force spectroscopy to study the mechanical unfolding pathways of maltose binding protein (MBP) and its precursor protein (preMBP) in the presence and absence of ligands. Our results show that MBP exhibits kinetic partitioning on mechanical stretching and unfolds via two parallel pathways: one of them involves a mechanically stable intermediate (path I) while the other is devoid of it (path II). The apoMBP unfolds via path I in 62% of the mechanical unfolding events and the remaining 38% follow path II. In the case of maltose bound MBP, the protein unfolds via the intermediate in 79% of the cases, the remaining 21% via path II. Similarly, on binding to maltotriose, a ligand whose binding strength with the polyprotein is similar to that of maltose, the occurrence of the intermediate is comparable (82% via path I) to that of maltose. The precursor protein preMBP also shows a similar behaviour upon mechanical unfolding. The percentages of molecules unfolding via path I are 53% in the apo form and 68% and 72% upon binding to maltose and maltotriose, respectively for preMBP