From Hypothesis
To Conclusion
Cost effective Cheminformatics for Small
Chemistry Teams Integrated Within
Larger Discovery Groups
John McNeil
September 15, 2009
1
“We make tools to help bench scientists be more
productive, efficient, and creative.”
Integrate Technology
Invent solutions
Bioinformatics
Manage IT
2
From Hypothesis
LabSynch Overview
To Conclusion
• Objectives
Record better information with less work
-
Share complete methods and data in context
is a fully integrated:
• LabSynch
Electronic lab notebook
- Collaboration web service
- Sample tracking system
- Data capture and analysis tool
•
LabSynch is Open Source (GPLv2)
3
From Hypothesis
What is LabSynch?
To Conclusion
LabSynch
LabSynch
Page
LabSynch
Page
LabSynch
Page
LabSynch
Page
LabSynch
Page
Page
LabSynch
Page
1
Wiki Pages
3
R Statistical
Programming Language
LabSynch
Database
2
Flexible LIMS
Database
External
Database
4 External
Database
4
From Hypothesis
To Conclusion
LabSynch at Ambrx, Inc.
5
From Hypothesis
To Conclusion
Molecular Biology
6
From Hypothesis
To Conclusion
Custom Request/Report System
7
From Hypothesis
To Conclusion
Protein Analytics
8
From Hypothesis
Dose Response Fitting
To Conclusion
To Print
https://host.labsynch.com/labsynchdemo/skin/printWindow.html
Plate Map (xls)
Plate Data (.txt)
[1] "
Super
Super Assay::ec50
Assay::curveFlag
Units
()
Thing
Value
Super
Assay::slope
( [ng/mL] )
Super
Super
Super
Assay::empirMax Assay::empirAvgMax Assay::curveMax
( Hill )
( RFU )
( RFU )
Value Uncertainty Value Uncertainty Value Uncertainty Value
LOT:
weak tested
MCL-000-004 potency
NA
LOT:
passed
MCL-000-003
LOT:
passed
MCL-000-001
none
-1.47
0.796
0.823 0
276.134 139.766
-0.989 0.228
2.757
-1.286 0.25
0.475
Super
Super
Super
Super
Assay::empirMin Assay::empirAvgMin Assay::curveMin Assay::Rsquared
( RFU )
( RFU )
( RFU )
Uncertainty Value Uncertainty Value Uncertainty Value
0.796
0.038
1.056 0
1.034
1.238 0
1.183
( RFU )
()
Uncertainty Value Uncertainty
Value
1.103 0.982
0.55
0
0.554
0.006
0.595 0.008
0.81
0.031
1.139 0.104
0.589 0
0.609
0.028
0.626 0.01
0.956
0.078
1.194 0.025
0.593 0
0.639
0.066
0.651 0.018
0.967
From Hypothesis
To Conclusion
"
[1]
Super Assay
Sample
Lot
9
EC50 [ng/mL] Relative Potency (%) X-fold Less Activity
Mut_1
Material: LOT MCL-000-004 NA
NA
NA
Mut_2
Material: LOT MCL-000-003 276.134
1
100.16
WT
Material: LOT MCL-000-001 2.757
100
1
BioAssay Output File (right click to download output data .csv file)
2 of 3
From Hypothesis
2/16/09 11:10 AM
Automated PK/PD Analysis
To Conclusion
Plate
Layout
Template
Study Design
Wizard
Reader
Reader
Data
Reader
Data
Data
Plate Setup
Plate Analysis
Plate Analysis
Plate Analysis
sample
labels
PDF
animals
animals
samples
samples
samples
Re-Assay
Plate Analysis
Report
10
From Hypothesis
To Conclusion
Problem
• Chemists want compound organization,
batch tracking, sub-structure searching
• Biologists want complete history of lots,
including small molecules and conjugates
• LabSynch’s database is not structure-aware
11
From Hypothesis
To Conclusion
Solution = LabSynch + JChem
Step One
12
From Hypothesis
To Conclusion
Solution = LabSynch + JChem
Step Two
13
From Hypothesis
To Conclusion
Solution = LabSynch + JChem
Batch Registration
Compound Batch Registration
Automatically filled in if an
existing structure is
entered in marvin sketch.
14
From Hypothesis
To Conclusion
Solution = LabSynch + JChem
Resulting LabSynch Page
LabSynch
ID
External ID 21
IJC
Compound
ID
15
From Hypothesis
To Conclusion
Behind the Scenes
JChem Base
<iframe>
JSP
Structure Form
Embedded JS
Tomcat
Redirect
<iframe>
PHP
Batch Form
Embedded JS
MySQL
LabSynch
Server
PHP
16
From Hypothesis
To Conclusion
Connecting JChem JSP to LabSynch PHP
After registering a structure, the Structure form redirects the iframe to a
LabSynch form, passing the compound ID of the structure as a query parameter
if (structureAdded){ // new structure was created, redirect user to compound registration step
String redirectURL = serverBase + "/server/IJC_CompoundRegistration.php?cd_id=" + insertedId;
response.sendRedirect(redirectURL);
} else { // existing structure was found, redirect user to compound batch registration step
String redirectURL = serverBase + "/server/IJC_CompoundBatchRegistration.php?cd_id=" + insertedId;
response.sendRedirect(redirectURL);
}
If the user enters a structure that has already been registered, the
compound ID for that structure is returned, and the iframe is redirected
to the Compound Batch Registration form instead of Compound
Registration
17
From Hypothesis
To Conclusion
Future: Cross Linking
Java Web Start
Open URL in Browser
18
From Hypothesis
Summary
To Conclusion
•
IJC and JChem Base provide cost-effective tools for small groups
-
Low entry barrier – buy what we need
Simple server set-up – uses existing LabSynch server and
backup systems
•
Adding structure Items to LabSynch was straight-forward using
JChem Base and LabSynch API
•
•
•
Structure Items work in both IJC and LabSynch
No changes were required to existing biology forms and data
Users get new capability – science is tracked and shared better
19
From Hypothesis
Thanks To
To Conclusion
Ambrx
•
•
•
•
•
•
Melanie Nelson, Ph. D.
Zhenwei Miao, Ph. D.
Junjie Liu, Ph. D.
John McNeil & Co., Inc.
•
•
•
On Khongsaly
Guy Oshiro, Ph. D.
Matthew Shaw
Ying Sun, Ph. D.
Mike Trout
Bruce Kimmel, Ph. D.
20