Large Language Models and Genomics for Summarizing the Role of microRNA in Regulating mRNA Expression.

microRNA (miRNA)-messenger RNA (mRNA or gene) interactions are pivotal in various biological processes, including the regulation of gene expression, cellular differentiation, proliferation, apoptosis, and development, as well as the maintenance of cellular homeostasis and pathogenesis of numerous diseases, such as cancer, cardiovascular diseases, neurological disorders, and metabolic conditions. Understanding the mechanisms of miRNA-mRNA interactions can provide insights into disease mechanisms and potential therapeutic targets. However, extracting these interactions efficiently from a huge collection of published articles in PubMed is challenging. In the current study, we annotated a miRNA-mRNA Interaction Corpus (MMIC) and used it for evaluating the performance of a variety of machine learning (ML) models, deep learning-based transformer (DLT) models, and large language models (LLMs) in extracting the miRNA-mRNA interactions mentioned in PubMed. We used the genomics approaches for validating the extracted miRNA-mRNA interactions. Among the ML, DLT, and LLM models, PubMedBERT showed the highest precision, recall, and F-score, with all equal to 0.783. Among the LLM models, the performance of Llama-2 is better when compared to others. Llama 2 achieved 0.56 precision, 0.86 recall, and 0.68 F-score in a zero-shot experiment and 0.56 precision, 0.87 recall, and 0.68 F-score in a three-shot experiment. Our study shows that Llama 2 achieves better recall than ML and DLT models and leaves space for further improvement in terms of precision and F-score.

Accurate, Robust, and Scalable Machine Abstraction of Mayo Endoscopic Subscores From Colonoscopy Reports.

BACKGROUND: The Mayo endoscopic subscore (MES) is an important quantitative measure of disease activity in ulcerative colitis. Colonoscopy reports in routine clinical care usually characterize ulcerative colitis disease activity using free text description, limiting their utility for clinical research and quality improvement. We sought to develop algorithms to classify colonoscopy reports according to their MES. METHODS: We annotated 500 colonoscopy reports from 2 health systems. We trained and evaluated 4 classes of algorithms. Our primary outcome was accuracy in identifying scorable reports (binary) and assigning an MES (ordinal). Secondary outcomes included learning efficiency, generalizability, and fairness. RESULTS: Automated machine learning models achieved 98% and 97% accuracy on the binary and ordinal prediction tasks, outperforming other models. Binary models trained on the University of California, San Francisco data alone maintained accuracy (96%) on validation data from Zuckerberg San Francisco General. When using 80% of the training data, models remained accurate for the binary task (97% [n = 320]) but lost accuracy on the ordinal task (67% [n = 194]). We found no evidence of bias by gender (P = .65) or area deprivation index (P = .80). CONCLUSIONS: We derived a highly accurate pair of models capable of classifying reports by their MES and recognizing when to abstain from prediction. Our models were generalizable on outside institution validation. There was no evidence of algorithmic bias. Our methods have the potential to enable retrospective studies of treatment effectiveness, prospective identification of patients meeting study criteria, and quality improvement efforts in inflammatory bowel diseases.

Our accurate pair of models automatically classify colonoscopy reports by Mayo endoscopic subscore and abstain from prediction appropriately. Our methods can enable large-scale electronic health record studies of treatment effectiveness, prospective identification of patients for clinical trials, and quality improvement efforts in ulcerative colitis.

Real-world effectiveness of ustekinumab and vedolizumab in TNF-exposed pediatric patients with ulcerative colitis.

OBJECTIVES: Vedolizumab (VDZ) and ustekinumab (UST) are second-line treatments in pediatric patients with ulcerative colitis (UC) refractory to antitumor necrosis factor (anti-TNF) therapy. Pediatric studies comparing the effectiveness of these medications are lacking. Using a registry from ImproveCareNow (ICN), a global research network in pediatric inflammatory bowel disease, we compared the effectiveness of UST and VDZ in anti-TNF refractory UC. METHODS: We performed a propensity-score weighted regression analysis to compare corticosteroid-free clinical remission (CFCR) at 6 months from starting second-line therapy. Sensitivity analyses tested the robustness of our findings to different ways of handling missing outcome data. Secondary analyses evaluated alternative proxies of response and infection risk. RESULTS: Our cohort included 262 patients on VDZ and 74 patients on UST. At baseline, the two groups differed on their mean pediatric UC activity index (PUCAI) (p = 0.03) but were otherwise similar. At Month 6, 28.3% of patients on VDZ and 25.8% of those on UST achieved CFCR (p = 0.76). Our primary model showed no difference in CFCR (odds ratio: 0.81; 95% confidence interval [CI]: 0.41-1.59) (p = 0.54). The time to biologic discontinuation was similar in both groups (hazard ratio: 1.26; 95% CI: 0.76-2.08) (p = 0.36), with the reference group being VDZ, and we found no differences in clinical response, growth parameters, hospitalizations, surgeries, infections, or malignancy risk. Sensitivity analyses supported these findings of similar effectiveness. CONCLUSIONS: UST and VDZ are similarly effective for inducing clinical remission in anti-TNF refractory UC in pediatric patients. Providers should consider safety, tolerability, cost, and comorbidities when deciding between these therapies.