Design and Analysis Strategies for Pooling in High Throughput Screening: Application to the Search for a New Anti-Microbial

TL;DR

This paper evaluates various pooling strategies in high-throughput screening to improve the efficiency of discovering new antimicrobial agents, highlighting practical guidance through real-world applications.

Contribution

It provides a comprehensive analysis of recent pooling methods and screening analysis techniques, offering practical recommendations for antimicrobial drug discovery.

Findings

Pooling methods can increase screening efficiency

Certain pooling strategies outperform individual testing in specific scenarios

Challenges include false positives and complex data analysis

Abstract

A major public health issue is the growing resistance of bacteria to antibiotics. An important part of the needed response is the discovery and development of new antimicrobial strategies. These require the screening of potential new drugs, typically accomplished using high-throughput screening (HTS). Traditionally, HTS is performed by examining one compound per well, but a more efficient strategy pools multiple compounds per well. In this work, we study several recently proposed pooling construction methods, as well as a variety of pooled high-throughput screening analysis methods, in order to provide guidance to practitioners on which methods to use. This is done in the context of an application of the methods to the search for new drugs to combat bacterial infection. We discuss both an extensive pilot study as well as a small screening campaign, and highlight both the successes and challenges of the pooling approach.