Influenced by breakthroughs in LLMs, single-cell foundation models are emerging. While these models show successful performance in cell type clustering, phenotype classification, and gene perturbation response prediction, it remains to be seen if a simpler model could achieve comparable or better results, especially with limited data. This is important, as the quantity and quality of single-cell data typically fall short of the standards in textual data used for training LLMs. Single-cell sequencing often suffers from technical artifacts, dropout events, and batch effects. These challenges are compounded in a weakly supervised setting, where the labels of cell states can be noisy, further complicating the analysis. To tackle these challenges, we present sc-OTGM, streamlined with less than 500K parameters, making it approximately 100x more compact than the foundation models, offering an efficient alternative. sc-OTGM is an unsupervised model grounded in the inductive bias that the scRNAseq data can be generated from a combination of the finite multivariate Gaussian distributions. The core function of sc-OTGM is to create a probabilistic latent space utilizing a GMM as its prior distribution and distinguish between distinct cell populations by learning their respective marginal PDFs. It uses a Hit-and-Run Markov chain sampler to determine the OT plan across these PDFs within the GMM framework. We evaluated our model against a CRISPR-mediated perturbation dataset, called CROP-seq, consisting of 57 one-gene perturbations. Our results demonstrate that sc-OTGM is effective in cell state classification, aids in the analysis of differential gene expression, and ranks genes for target identification through a recommender system. It also predicts the effects of single-gene perturbations on downstream gene regulation and generates synthetic scRNA-seq data conditioned on specific cell states.

Inferring knowledge from clinical trials using knowledge graph embedding is an emerging area. However, customizing graph embeddings for different use cases remains a significant challenge. We propose custom2vec, an algorithmic framework to customize graph embeddings by incorporating user preferences in training the embeddings. It captures user preferences by adding custom nodes and links derived from manually vetted results of a separate information retrieval method. We propose a joint learning objective to preserve the original network structure while incorporating the user's custom annotations. We hypothesize that the custom training improves user-expected predictions, for example, in link prediction tasks. We demonstrate the effectiveness of custom2vec for clinical trials related to non-small cell lung cancer (NSCLC) with two customization scenarios: recommending immuno-oncology trials evaluating PD-1 inhibitors and exploring similar trials that compare new therapies with a standard of care. The results show that custom2vec training achieves better performance than the conventional training methods. Our approach is a novel way to customize knowledge graph embeddings and enable more accurate recommendations and predictions.

FDA has been promoting enrollment practices that could enhance the diversity of clinical trial populations, through broadening eligibility criteria. However, how to broaden eligibility remains a significant challenge. We propose an AI approach to Cohort Optimization (AICO) through transformer-based natural language processing of the eligibility criteria and evaluation of the criteria using real-world data. The method can extract common eligibility criteria variables from a large set of relevant trials and measure the generalizability of trial designs to real-world patients. It overcomes the scalability limits of existing manual methods and enables rapid simulation of eligibility criteria design for a disease of interest. A case study on breast cancer trial design demonstrates the utility of the method in improving trial generalizability.

An accurate problem list plays the key role of a problem-oriented medical record, which plays a significant role in improving patient care. However, the multi-author, multi-purpose nature of problem list makes it a challenge to maintain, and a single list is difficult, if not impossible, to satisfy all the needs of different practitioners. In this paper, we propose using machine generated problem list to assist a medical practitioner to review a patient’s chart. The proposed system scans both structured and unstructured data in a patient’s electronic medical record (EMR) and generates a ranked, recall-oriented problem list grouped by body systems. Details of each problem are readily available for the user to assess the correctness and relevance of the problem. The user can then provide feedback to the system on the trustworthiness of each evidence passage retrieved, as well as the validity of the problem as a whole. The user-specific feedback provides new information the system needs to perform active learning to learn the user’s preference and produce personalized, and/or domain-specific problem lists.

Identifying a patient’s important medical problems requires broad and deep medical expertise, as well as significant time to gather all the relevant facts from the patient’s medical record and assess the clinical importance of the facts in reaching the final conclusion. A patient’s medical problem list is by far the most critical information that a physician uses in treatment and care of a patient. In spite of its critical role, its curation, manual or automated, has been an unmet need in clinical practice. We developed a machine learning technique in IBM Watson to automatically generate a patient’s medical problem list. The machine learning model uses lexical and medical features extracted from a patient’s record using NLP techniques. We show that the automated method achieves 70% recall and 67% precision based on the gold standard that medical experts created on a set of de-identified patient records from a major hospital system in the US. To the best of our knowledge this is the first successful machine learning/NLP method of extracting an open-ended patient’s medical problems from an Electronic Medical Record (EMR). This paper also contributes a methodology for assessing accuracy of a medical problem list generation technique.