Project description:How to design experiments that accelerate knowledge discovery on complex biological landscapes remains a tantalizing question. Here, we present OPEX, an optimal experimental design method to identify informative omics experiments for both experimental space exploration and model training. OPEX-guided exploration of Escherichia coli's cross-behavior potential, when exposed to novel biocide and antibiotic combinations, led to accelerated knowledge discovery with predictive models that are more accurate while needing 44% fewer data to train. Selecting experiments favoring broader exploration followed by fine-tuning emerged as the optimal strategy. This led to the discovery of 29 cross-protection and 4 cross-vulnerability conditions, with further validation revealing the central role of chaperones, stress response proteins and transport pumps in cross-stress exposure. This work demonstrates how active learning can be used to automate omics data collection for training accurate predictive models, evidence-driven decision making and accelerated knowledge discovery in life sciences.
Project description:We report the application of single-cell RNA sequencing(scRNA-seq) in mouse monocyte cells by integrating scRNA-seq, transcriptionfactor binding motifs, and ATAC-seq data using machine learning. We generated scRNA-seqdata from mouse monocytes treated with PBS, SD-LPS, 4-PBA, and SD-LPS + 4-PBA tounderstand the gene regulatory networks of monocytes under the low-grade inflammatorycondition and the mechanism of action for 4-PBA. We find two novelsubpopulations of monocyte cells in response to SD-LPS. We show that 4-PBApotently reprograms an anti-inflammatory monocyte phenotype and masks theeffects of subclinical low dose LPS. Together with TF binding motifs and ATAC-seqdata, a machine learning method, using guided, regularized random forest (GRRF)and feature selection was developed to select the best candidate TFs that areinvolved in the activation of monocytes within different clusters. Our results suggestthat our new machine learning method can select candidate regulatory genes aspotential targets for developing new therapeutics against low-gradeinflammation.
Project description:Development of a novel machine learning guided ctDNA detection platform for use in liquid biopsy detection and therapeutic monitoring of solid tumors in several clinical contexts. Included are WGS alignments from our study.
