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Autonomous model building with a preponderance
of well annotated assay protocols
Alex M. Clark
http://www.bioassayexpress.com
⚡
COLLABORATIVE DRUG DISCOVERY
Background
◈ Assay protocols are text
◈ Institutions suffering from

data overload:
▷ much interest in using 

consistent markup
▷ semantic web ontologies: 

BAO, DTO, CLO, GO...
◈ Since last talk: many refinements, some new
structure-activity analysis features
2
Cell-Free Homogeneous Primary HTS to Identify
Inhibitors of GSK3beta Activity
(1) Dispense 1 uL/well of CABPE, 0.5 uL of ATP, and
1 uL of positive control GW8510 or AB in
respective wells according to plate design to
1536-well assay ready plates (Aurora 29847) that
contain 2.5 nL/well of 10 mM compound using
BioRAPTR (Beckman) to start the reaction.
Incubate at room temperature for 60 minutes.
(2) Add 2.5 uL/well of ADP-glo (Promega, V9103)
with BioRAPTR, incubate at room temperature for
40 minutes
(3) Add 5 uL/well of ADP-glo (Promega, V9103) with
Combi nL (Thermo), incubate at room
temperature for 30 minutes
Curation
◈ Web UI
◈ Machine
learning
◈ Common
Assay
Template
◈ PubChem
data
3
Public Data
◈ Designed Common Assay
Template for summary
◈ Data from PubChem:
▷ 3500 assays selected
▷ mostly MLPCN
◈ Curated as a validation set
◈ PubChem also has
molecules...
4
Analysis
◈ Selected:
▷ Secondary assays
▷ Infectious diseases
▷ IC50 results
5
Analysis
◈ Selected:
▷ Secondary assays
▷ Infectious diseases
▷ IC50 results
5
Molecules
◈ Per assay: convenient way to view & download...
6
Groups of Assays
7
Bayesian Models
8
Bayesian Models
8
Bayesian Models
8
Bayesian Models
8
Proposed Molecules
9
Proposed Molecules
9
Proposed Molecules
9
Proposed Molecules
9
Iterative Structures
10
Iterative Structures
10
Iterative Structures
10
Grids
◈ View known & calculated measurements, plotting
assays vs. compounds...
11
Grids
◈ View known & calculated measurements, plotting
assays vs. compounds...
11
Real Data Only
12
◈ Assays are singletons by default, can be grouped...
Real Data Only
12
Filling in Blanks
13
Filling in Blanks
13
◈ Bayesian model created
for each column
◈ SAR for all assays used
◈ Missing cells replaced
with predictions
◈ Calculations realtime:
▷ model on server
▷ predictions on client
Trend Detection
14
◈ Model compound found using the
Selectivity option:
Trend Detection
14
◈ Model compound found using the
Selectivity option: multidrug resistant
tuberculosis
Trend Detection
14
◈ Model compound found using the
Selectivity option: multidrug resistant
tuberculosis trypanosomiasis
(ROC 0.56)
Possible Interest
15
Possible Interest
15
Future Work
◈ Current focus is UI/UX and proof-of-concept...
▷ intensive data mining is next: annotations + SAR
▷ data is ready to reveal some amazing discoveries
◈ Crowd curation may be necessary, and more detailed
templates
◈ More modelling techniques, far beyond Bayesians:
parallel project is underway...
16
Deployment
◈ Public
▷ http://www.bioassayexpress.com
▷ http://beta.bioassayexpress.com (curation)
◈ Vault
▷ sync with CDD Vault through API
◈ Private
▷ custom integration, installed behind firewall
17
Acknowledgments
◈ Collaborative Drug Discovery
⇨ Barry Bunin
⇨ Janice Kranz
⇨ Hande Küçük
⇨ Peter Gedeck
18
◈ And we're hiring
⇨ resumes to:
◈ More information
http://github.com/cdd/bioassay-template
http://www.bioassayexpress.com
http://collaborativedrug.com
alex@collaborativedrug.com

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