Combi-seq for multiplexed transcriptome-based profiling of drug combinations using deterministic barcoding in single-cell droplets.

Anti-cancer therapies often exhibit only short-term effects. Tumors typically develop drug resistance causing relapses that might be tackled with drug combinations. Identification of the right combination is challenging and would benefit from high-content, high-throughput combinatorial screens directly on patient biopsies. However, such screens require a large amount of material, normally not available from patients. To address these challenges, we present a scalable microfluidic workflow, called Combi-Seq, to screen hundreds of drug combinations in picoliter-size droplets using transcriptome changes as a readout for drug effects. We devise a deterministic combinatorial DNA barcoding approach to encode treatment conditions, enabling the gene expression-based readout of drug effects in a highly multiplexed fashion. We apply Combi-Seq to screen the effect of 420 drug combinations on the transcriptome of K562 cells using only ~250 single cell droplets per condition, to successfully predict synergistic and antagonistic drug pairs, as well as their pathway activities.

Evolution of Lotka-Volterra predator-prey systems under telegraph noise.

In this paper we study a Lotka-Volterra predator-prey system with prey logistic growth under the telegraph noise. The telegraph noise switches at random two prey-predator models. The aim of this work is to determine the subset of omega-limit set of the system and show out the existence of a stationary distribution. We also focus on persistence of the predator and thus we look for conditions that allow persistence of the predator and prey community. We show that the asymptotic behaviour highly depends on the value of some constant lambda which is useful to make suitable predictions about the persistence of the system.