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This presentation covers the concepts of functional genomics and the use of the TCL Job Compiler in genomics research. It includes an overview of the single-gene deletion strategy and the applications of functional genomics in discovering new vaccines, identifying causes of diseases, and understanding genetic structure and evolution.
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Reengineering the TCL Job Compiler SEM49060 Project Talk Ben Tagger 8th May 2003
Structure of Today’s Presentation • Introduction • Functional Genomics • Single-gene Deletion • The Robot Scientist • The TCL Job Compiler • Conclusion/Future
Aims of the Talk • What was done • Why it was important to do it • How it was done
Functional Genomics • Genomics can be split into 2 categories • Structural genomics • Functional genomics • Used for… • The discovery of new vaccines and drugs • Identification of causes of diseases • Understanding genetic structure and evolution • Establishing of common metabolic pathways
Methods in Functional Genomics • Various Techniques • Pairwise Alignment • Expression Profiling • Proteomics • Single-gene Deletion • Auxotrophic experimentation using a single-gene deletion strategy.
Single-gene Deletion • Used to identify the function of an unknown gene. • Auxotrophic mutant organisms • Grown in different growth solution • Establish responsible enzyme for particular pathway.
An Example A Reaction R C B E G
The Robot Scientist • 3 Parts • ASE-Progol • TCL Job Compiler • Biomek Robot Workstation • … together form the Robot Scientist
ASE-Progol • Active Selection of Experiments with Progol. • Uses ILP to generate hypotheses • Selects experiments to eliminate these hypotheses • Composes Experiments for the Robot • Closed loop machine learning system
In more detail… • Hypothesis Generation • Trial Generation • Classifier • Trial Selection • Termination
Biomek Robot WorkStation • Beckman Coulter 2000 Workstation • Liquid handling station
1 2 3 4 5 6 A B Work Spaces • 12 locations – can be split up further
The TCL Job Compiler Expt.txt TCL RsConfig.txt Job Compiler Substances.txt Surface.txt Job0.txt . . . LOG JobN.txt
A1 VICTOR -51.8 33.9 78.1 1 A21 P20L A6 quarter vertical B2 P20 B3 96-well flat A6A1 YBR166C:E-2 20000.0 A6A2 C00078:2E-1 20000.0 A6A3 YDR035W:E-2 20000.0 B5A1 C00108:2E-1 20000.0 B5A2 C00166:2E-1 20000.0 B5A3 YDR007W:E-2 20000.0 Surface File
Experiment file # B1, minimal-agar 120, time 57600, # E9, minimal-agar 120, YDR354W:E-2 20, C00108:2E-1 20, time 57600,
Log "Executing LiquidTransfer: 0" Tool attach P20L Log "Attaching tip P20 with some grid reference (not sure yet)" Tip attach dispose P20 P20 P20L Log "Attaching to P20 with some grid reference (not sure yet)" Move Abs [Coord B5 A2] 46.872 Log "Checking volumes: 19960.0 23600.0" Log "Aspirating C00166:2E-1 from B5A2 (volume 20.0)" Move Abs T 15.6502 Move Abs Z 9.2696 putres system pod dirty_tip 1 Move Rel T 17.8872 Delay 0 Move Abs Z 44.87 Move Abs T 15.6502 Delay 0 Move Abs T 9.0 Delay 0 Move Abs T 15.6502 Move Abs Z 9.2696 putres system pod dirty_tip 1 Move Rel T 14.5822 Delay 0 Move Rel T -1.322 Move Abs Z 46.872 Move Abs [Coord A4 A4] 22.167 Log "Checking volumes: 20.0 362.76" PutVal tools P20L max_velocity 2 Move Abs Z 18.5725 Move Abs T 15.6502 PutVal tools P20L max_velocity 25.0 Delay 0 Move Abs Z 20.17 Move Abs T 9.0 Delay 0 Log "Transfer from B5 A2 to A4 A4, C00166:2E-1, Volume: 20.0 COMPLETE." A Single Liquid Transfer
Conclusion • It works! – Success… • Changes to Experiment File • Needs Further Testing • Acceptance Testing • System Analysis