A Multimodal Data Analysis Approach for Targeted Drug Discovery Involving Topological Data Analysis (TDA).
In silico drug discovery refers to a combination of computational techniques that augment our ability to discover drug compounds from compound libraries. Many such techniques exist, including virtual high-throughput screening (vHTS), high-throughput screening (HTS), and mechanisms for data storage and querying. However, presently these tools are often used independent of one another. In this chapter, we describe a new multimodal in silico technique for the hit identification and lead generation phases of traditional drug discovery. Our technique leverages the benefits of three independent methods-virtual high-throughput screening, high-throughput screening, and structural fingerprint analysis-by using a fourth technique called topological data analysis (TDA). We describe how a compound library can be independently tested with vHTS, HTS, and fingerprint analysis, and how the results can be transformed into a topological data analysis network to identify compounds from a diverse group of structural families. This process of using TDA or similar clustering methods to identify drug leads is advantageous because it provides a mechanism for choosing structurally diverse compounds while maintaining the unique advantages of already established techniques such as vHTS and HTS.
Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Muthuraman
M
Alagappan
Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Dadi
D
Jiang
Department of Radiation Oncology, Wexner Medical Center and Comprehensive Cancer Center, Ohio State University, Columbus, OH, 43210, USA.
Nicholas
N
Denko
Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, 94305, USA. akoong@stanford.edu.
Albert C
AC
Koong
D055808:Drug Discovery / Q000379:methods*; D057166:High-Throughput Screening Assays; D054852:Small Molecule Libraries / Q000032:analysis; D013223:Statistics as Topic; D014584:User-Computer Interface
D054852:Small Molecule Libraries
Computer aided drug discovery; Fingerprint; High-throughput screening; In silico; Topological data analysis; Virtual screening