Genomic and Synthetic Biology Digital Biosecurity.

Trends toward automation of synthetic biology and the individualization of biology and medicine raise varied and critical security issues. Digital biosecurity brings together researchers working in secure algorithms, vulnerability assessments, and emerging threat models. The fundamental goal of this digital biosecurity workshop is to identify and present distinct areas of research around making the next generation of biology safer and more secure. The workshop will include a panel overview of the field, including representatives from academia, industry, and non-profits. It will also include novel presentations from the research community. We expect that attendees will leave this workshop with a new appreciation of the research and implementation challenges in maintaining the digital aspects of biosecurity.

Machine Learning Helps Identify New Drug Mechanisms in Triple-Negative Breast Cancer.

This paper demonstrates the ability of mach- ine learning approaches to identify a few genes among the 23,398 genes of the human genome to experiment on in the laboratory to establish new drug mechanisms. As a case study, this paper uses MDA-MB-231 breast cancer single-cells treated with the antidiabetic drug metformin. We show that mixture-model-based unsupervised methods with validation from hierarchical clustering can identify single-cell subpopulations (clusters). These clusters are characterized by a small set of genes (1% of the genome) that have significant differential expression across the clusters and are also highly correlated with pathways with anticancer effects driven by metformin. Among the identified small set of genes associated with reduced breast cancer incidence, laboratory experiments on one of the genes, CDC42, showed that its downregulation by metformin inhibited cancer cell migration and proliferation, thus validating the ability of machine learning approaches to identify biologically relevant candidates for laboratory experiments. Given the large size of the human genome and limitations in cost and skilled resources, the broader impact of this work in identifying a small set of differentially expressed genes after drug treatment lies in augmenting the drug-disease knowledge of pharmacogenomics experts in laboratory investigations, which could help establish novel biological mechanisms associated with drug response in diseases beyond breast cancer.

Prediction of adenocarcinoma development using game theory.

Recent research shows that gene expression changes appear to correlate well with the progression of many types of cancers. Using changes in gene expression as a basis, this paper proposes a data-driven 2-player game-theoretic model to predict the risk of adenocarcinoma based on Nash equilibrium. A key innovation in this work is the pay-off function which is a weighted composite of the expression of a cohort of tumor-suppressor genes (as one player) and an analogous cohort of oncogenes (as the other player). Another novelty of the model is its ability to predict the risk that a healthy sample will develop adenocarcinoma, if its associated gene expression is comparable to that of early-stage tumor samples. The model is validated using two of the largest publicly available adenocarcinoma datasets. The results show that i) the model is able to distinguish between healthy and cancerous samples with an accuracy of 93%, and ii) 95% of the healthy samples said to be at risk had gene expressions comparable to those of samples with stage I or stage II tumors, thereby predicting the imminent onset of adenocarcinoma.