SIC50: Determining drug inhibitory concentrations using a vision transformer and an optimized Sobel operator

Yongheng Wang; Weidi Zhang; Hoyin Yip; Chuyuan Qu; Hongru Hu; Xiaotie Chen; Teresa Lee; Xi Yang; Bingjun Yang; Priyadarsini Kumar; Su Yeon Lee; Javier J Casimiro; Jiawei Zhang; Aijun Wang; Kit S Lam

doi:10.1016/j.patter.2023.100686

SIC50: Determining drug inhibitory concentrations using a vision transformer and an optimized Sobel operator

Patterns (N Y). 2023 Feb 3;4(2):100686. doi: 10.1016/j.patter.2023.100686. eCollection 2023 Feb 10.

Authors

Yongheng Wang¹, Weidi Zhang², Hoyin Yip², Chuyuan Qu³, Hongru Hu⁴, Xiaotie Chen⁵, Teresa Lee⁶, Xi Yang⁷, Bingjun Yang², Priyadarsini Kumar^{2

8}, Su Yeon Lee², Javier J Casimiro², Jiawei Zhang⁹, Aijun Wang^{1

2

8}, Kit S Lam^{10

11}

Affiliations

¹ Department of Biomedical Engineering, University of California, Davis, Davis, CA 95616, USA.
² Center for Surgical Bioengineering, Department of Surgery, University of California, Davis, School of Medicine, Sacramento, CA 95817, USA.
³ Microsoft, Redmond, WA 98052, USA.
⁴ Integrative Genetics and Genomics, University of California, Davis, Davis, CA 95616, USA.
⁵ Department of Mathematics, University of California, Davis, Davis, CA 95616, USA.
⁶ Department of Biomedical Engineering, Yale University, New Haven, CT 06511, USA.
⁷ Intel, Santa Clara, CA 95054, USA.
⁸ Institute for Pediatric Regenerative Medicine, Shriners Hospital for Children Northern California, UC Davis School of Medicine, Sacramento, CA 96817, USA.
⁹ Department of Computer Science, IFM Lab, University of California, Davis, Davis, CA 95616, USA.
¹⁰ Department of Biochemistry and Molecular Medicine, UC Davis NCI-designated Comprehensive Cancer Center, University of California, Davis, Sacramento, CA 95817, USA.
¹¹ Division of Hematology and Oncology, Department of Internal Medicine, School of Medicine, University of California, Davis, Sacramento, CA 95817, USA.

Abstract

As a measure of cytotoxic potency, half-maximal inhibitory concentration (IC50) is the concentration at which a drug exerts half of its maximal inhibitory effect against target cells. It can be determined by various methods that require applying additional reagents or lysing the cells. Here, we describe a label-free Sobel-edge-based method, which we name SIC50, for the evaluation of IC50. SIC50 classifies preprocessed phase-contrast images with a state-of-the-art vision transformer and allows for the continuous assessment of IC50 in a faster and more cost-efficient manner. We have validated this method using four drugs and 1,536-well plates and also built a web application. We anticipate that this method will assist in the high-throughput screening of chemical libraries (e.g., small-molecule drugs, small interfering RNA [siRNA], and microRNA and drug discovery).

Keywords: cancer drug potency; convolution neural network; vision transformer.

Grants and funding

R01 CA247685/CA/NCI NIH HHS/United States