Development and Validation of an Automated DNA-Encoded Library Screening Data Analysis Platform: PB-DEL Autoscreening...

Area of Science:

• Medicinal Chemistry
• Computational Biology
• Drug Discovery

Background:

• Current DNA-encoded library (DEL) analysis methods are often institute-specific, focusing narrowly on protein-ligand interactions.
• Existing approaches neglect crucial factors like sequencing depth, error rates, and quality control in candidate compound identification.
• The subjective and time-consuming nature of current DEL data analysis hinders its application in discovering new drugs.

Purpose of the Study:

• To develop an integral, accurate, and automated analysis workflow for DNA-encoded library screening.
• To address limitations in existing DEL analysis, including tractability, sequencing quality, and compound recommendation subjectivity.
• To accelerate the identification of novel drug candidates through standardized computational and AI-driven analysis.

Main Methods:

• Developed an automated workflow integrating building block and DNA tag tractability analysis across split-and-pool cycles.
• Incorporated 2D and 3D plotting for enhanced data visualization and analysis.
• Utilized computational analysis, artificial intelligence, and medicinal chemistry expertise to construct an enriched compound list.

Main Results:

• The automated workflow demonstrated tractability of building blocks and DNA tags.
• Successfully identified novel hit compounds with high potency and selectivity against the CDK9 antitumor target.
• Achieved efficient identification of drug candidates with minimal synthetic effort, validating the workflow's effectiveness.

Conclusions:

• The developed automated workflow provides an accurate and standardized approach for DEL screening data analysis.
• This method significantly enhances the efficiency and objectivity of compound recommendation for drug discovery.
• The workflow facilitates the rapid identification of potent and selective drug candidates, accelerating novel therapeutic development.