Local generation and efficient evaluation of numerous drug combinations in a single sample

Abstract
Data availability
Article and author information
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Abstract

We develop a method that allows one to test a large number of drug combinations in a single cell culture sample. We rely on the randomness of drug uptake in individual cells as a tool to create and encode drug treatment regimens. A single sample containing thousands of cells is treated with a combination of fluorescently barcoded drugs. We create independent transient drug gradients across the cell culture sample to produce heterogeneous local drug combinations. After the incubation period, the ensuing phenotype and corresponding drug barcodes for each cell are recorded. We use these data for statistical prediction of the treatment response to the drugs in a macroscopic population of cells. To further application of this technology, we developed a fluorescent barcodingmethod that does not require any chemical drug(s) modifications. We also developed segmentation-free image analysis capable of handling large optical fields containing thousands of cells in the sample, even in confluent growth condition. The technology necessary to execute our method is readily available in most biological laboratories, does not require robotic or microfluidic devices, and dramatically reduces resource needs and resulting costs of the traditional high-throughput studies.

Data availability

Imaging, flow cytometry data, and custom Wolfram Mathematica computer code use for data analysis were deposited in Dryad database.

The following data sets were generated

1. Loscalzo J
2. Elgart V
(2022) Local Generation and Efficient Evaluation of Numerous Drug Combinations in a Single Sample
Dryad Digital Repository, doi:10.5061/dryad.76hdr7t1d.

https://dx.doi.org/10.5061/dryad.76hdr7t1d

Article and author information

Author details

Vlad Elgart

Department of Medicine, Brigham and Women's Hospital, Boston, United States

Competing interests
The authors declare that no competing interests exist.
Joseph Loscalzo

Department of Medicine, Brigham and Women's Hospital, Boston, United States

For correspondence
jloscalzo@rics.bwh.harvard.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-1153-8047

Funding

National Institutes of Health (HGHG007690)

Joseph Loscalzo

National Institutes of Health (HL108630)

Joseph Loscalzo

National Institutes of Health (HL155107)

Joseph Loscalzo

National Institutes of Health (HL155096)

Joseph Loscalzo

National Institutes of Health (HL119145)

Joseph Loscalzo

American Heart Association (D700382 and CV-19)

Joseph Loscalzo

American Heart Association (AHA957729)

Joseph Loscalzo

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.