Transcript SPIRIT: The Story of a LIMS

SPIRIT:
THE STORY OF A LIMS
Oliver Peter
Group Leader, HTS & Compound Management
Actelion Pharmaceuticals Ltd.
[email protected]
Copyright © 2015 Actelion Pharmaceuticals Ltd
ABSTRACT
SPIRIT: THE STORY OF A LIMS
(LABORATORY INFORMATION MANAGEMENT SYSTEM)
Biotech and pharmaceutical companies (and academic institutions!) generate value
primarily by producing knowledge, rather than actual goods. Managing research
data and harvesting the information contained therein is a crucial step on the way to
creating knowledge. Hence a powerful laboratory information management system
(LIMS) is eminently important for science-driven enterprises and academia. Yet
most appear to struggle with it.
This is the story of “SPIRIT”, Actelion’s second generation LIMS. I would like to
share with you how the need for a new LIMS arose; what its design principles are;
how we implemented them, and how the software was taken up by the scientists.
What did we achieve with this software, what lessons did we learn, and what plans
to we have with it? This is also an account of our first experiences with providing
SPIRIT to the University of Basel free for academic use.
2
© 2015 Actelion Pharmaceuticals Ltd
18 Jun 2015
Life Science Forum Basel 2015
ACTELION’S
DRUG DISCOVERY LIMS
1st Generation - The era of chemistry
3
© 2015 Actelion Pharmaceuticals Ltd
18 Jun 2015
Life Science Forum Basel 2015
FROM DISEASE TO DRUG
THE STANDARD DRUG DISCOVERY AND DEVELOPMENT PIPELINE
new
disease target assay hits lead
target
target HTS
discovery validation
H2L
LO
Precl i nical
Ca ndidate
Cl i nical
Ca ndidate
New Drug
Appl ication
PCC
CC
NDA
pre-clinical
testing
clinical phases
I / II / III
number of
compounds under investigation
in each project
running costs
per project
4
© 2015 Actelion Pharmaceuticals Ltd
18 Jun 2015
Life Science Forum Basel 2015
drug
OUR CORE BUSINESS
MULTIPARAMETRIC COMPOUND OPTIMIZATION
activity
"chemical space"
5
© 2015 Actelion Pharmaceuticals Ltd
18 Jun 2015
Life Science Forum Basel 2015
some parameters:
• activity on target
• activities off target
• solubility
• chemical stability
• CYP450 inhibition/induction
• hERG channel blockade
• metabolic stability
• bioavailability
• BBB penetration
• genotoxicity
OUR RESEARCH DATABASE “OSIRIS”
ITS STRUCTURE REFLECTS OUR INITIAL CORE BUSINESS
Activity
Compound
ID
Compound
Structure
β2-Adrenergic
Receptor
Inhibition
Histamine
Receptor
Inhibition
0000001
290 nM
0000002
> 25'000 nM
0000003
>25'000 nM >25'000 nM
Endothelin
Receptor
Inhibition
>25'000 nM > 25'000 nM
170 nM
>25'000 nM
5 nM
millions of
compounds
6
© 2015 Actelion Pharmaceuticals Ltd
18 Jun 2015
Life Science Forum Basel 2015
scores
of tests
DATA RETRIEVAL AND ANALYSIS
THE “DATAWARRIOR” SOFTWARE
7
© 2015 Actelion Pharmaceuticals Ltd
18 Jun 2015
Life Science Forum Basel 2015
WE HAVE A PROBLEM,
AND NOBODY SEES IT
8
© 2015 Actelion Pharmaceuticals Ltd
18 Jun 2015
Life Science Forum Basel 2015
WE WANT TO DEVELOP DRUGS!
WE WERE INHERENTLY FOCUSED ON COMPOUNDS
new
disease target assay hits lead
target
target HTS
discovery validation
9
© 2015 Actelion Pharmaceuticals Ltd
H2L
18 Jun 2015
LO
Precl i nical
Ca ndidate
Cl i nical
Ca ndidate
New Drug
Appl ication
PCC
CC
NDA
pre-clinical
testing
Life Science Forum Basel 2015
clinical phases
I / II / III
drug
BUT WHICH ARE THE RIGHT TARGETS?
FOCUS SHIFT FROM COMPOUNDS TO BIOLOGY
new
disease target assay hits lead
target
target HTS
discovery validation
H2L
LO
Precl i nical
Ca ndidate
Cl i nical
Ca ndidate
New Drug
Appl ication
PCC
CC
NDA
pre-clinical
testing
clinical phases
I / II / III
drug
1. The objects of these investigations are not chemical structures, but:
animals, humans, organs, tissues, cells - alive and in the form of preparations;
proteins, genes, pathways, complex reagents - more or les defined.
10
© 2015 Actelion Pharmaceuticals Ltd
18 Jun 2015
Life Science Forum Basel 2015
BUT WHICH ARE THE RIGHT TARGETS?
FOCUS SHIFT FROM COMPOUNDS TO BIOLOGY
new
disease target assay hits lead
target
target HTS
discovery validation
H2L
LO
Precl i nical
Ca ndidate
Cl i nical
Ca ndidate
New Drug
Appl ication
PCC
CC
NDA
pre-clinical
testing
clinical phases
I / II / III
drug
2. The variables of these investigations are complex and diverse:
marker occurrence, distribution, concentration; structure, shape, functional state;
symptoms, behaviour, feeling...
11
© 2015 Actelion Pharmaceuticals Ltd
18 Jun 2015
Life Science Forum Basel 2015
BUT WHICH ARE THE RIGHT TARGETS?
FOCUS SHIFT FROM COMPOUNDS TO BIOLOGY
new
disease target assay hits lead
target
target HTS
discovery validation
H2L
LO
Precl i nical
Ca ndidate
Cl i nical
Ca ndidate
New Drug
Appl ication
PCC
CC
NDA
pre-clinical
testing
clinical phases
I / II / III
drug
3. These investigations do not uncover an inherent property of an entity, but:
they establish the statistical likelihood of outcomes, aim to generate, corroborate
or falsify hypotheses. Context is everything!
12
© 2015 Actelion Pharmaceuticals Ltd
18 Jun 2015
Life Science Forum Basel 2015
WE HAVE A PROBLEM...
WE ONLY STORE COMPOUND ACTIVITIES IN A STRUCTURED WAY
Activity
Compound
ID
Compound
Structure
β2-Adrenergic
Receptor
Inhibition
Histamine
Receptor
Inhibition
0000001
290 nM
0000002
> 25'000 nM
0000003
>25'000 nM >25'000 nM
Endothelin
Receptor
Inhibition
>25'000 nM > 25'000 nM
170 nM
>25'000 nM
5 nM
 All other data is stored unstructured:
13
–
electronic lab journal (free text with some meta tags)
–
report document management system (scans of signed printouts)
© 2015 Actelion Pharmaceuticals Ltd
18 Jun 2015
Life Science Forum Basel 2015
WE HAVE A PROBLEM...
...AND NOBODY SEES IT!
14
treatment
bleo
bleo
bleo
bleo
bleo
bleo
bleo
bleo
bleo
bleo
bleo
bleo
bleo
bleo
bleo
bleo
bleo
bleo
bleo
bleo
bleo
bleo
bleo
bleo
bleo
bleo
bleo
bleo
bleo
bleo
bleo
bleo
bleo
bleo
bleo
animal
mouse 1
mouse 1
mouse 1
mouse 1
mouse 1
mouse 1
mouse 1
mouse 1
mouse 1
mouse 1
mouse 1
mouse 1
mouse 1
mouse 1
mouse 1
mouse 1
mouse 1
mouse 1
mouse 1
mouse 1
mouse 1
mouse 1
mouse 1
mouse 1
mouse 1
mouse 1
mouse 1
mouse 1
mouse 1
mouse 1
mouse 1
mouse 1
mouse 2
mouse 2
mouse 2
assay
timepoint
QPCR
1
QPCR
1
QPCR
1
QPCR
1
QPCR
2
QPCR
2
QPCR
2
QPCR
2
QPCR
3
QPCR
3
QPCR
3
QPCR
3
QPCR
4
QPCR
4
QPCR
4
QPCR
4
quant imm assays
1
quant imm assays
1
quant imm assays
1
quant imm assays
1
quant imm assays
2
quant imm assays
2
quant imm assays
2
quant imm assays
2
quant imm assays
3
quant imm assays
3
quant imm assays
3
quant imm assays
3
quant imm assays
4
quant imm assays
4
quant imm assays
4
quant imm assays
4
QPCR
1
QPCR
1
QPCR
1
© 2015 Actelion Pharmaceuticals Ltd
18 Jun 2015
analyte
RNA 1
RNA 2
RNA 3
RNA 4
RNA 1
RNA 2
RNA 3
RNA 4
RNA 1
RNA 2
RNA 3
RNA 4
RNA 1
RNA 2
RNA 3
RNA 4
protein 1
protein 2
protein 3
protein 4
protein 1
protein 2
protein 3
protein 4
protein 1
protein 2
protein 3
protein 4
protein 1
protein 2
protein 3
protein 4
RNA 1
RNA 2
RNA 3
value 1
49
51
42
63
50
55
44
49
51
42
63
50
55
44
63
50
55
44
49
51
42
63
49
51
42
63
50
55
44
63
50
55
44
49
51
value 2
63
50
55
44
49
51
42
63
50
55
44
63
50
55
44
49
51
42
63
49
51
42
63
50
55
44
63
50
55
44
49
51
42
42
63
Life Science Forum Basel 2015
gene
gene 1
gene 2
gene 3
gene 4
gene 1
gene 2
gene 3
gene 4
gene 1
gene 2
gene 3
gene 4
gene 1
gene 2
gene 3
gene 4
gene 1
gene 2
gene 3
gene 4
gene 1
gene 2
gene 3
gene 4
gene 1
gene 2
gene 3
gene 4
gene 1
gene 2
gene 3
gene 4
gene 1
gene 2
gene 3
pathway
pathway 1
pathway 1
pathway 1
pathway 1
pathway 1
pathway 1
pathway 1
pathway 1
pathway 1
pathway 1
pathway 1
pathway 1
pathway 1
pathway 1
pathway 1
pathway 1
pathway 1
pathway 1
IVV-20-09:
11‘230 results
WE HAVE A PROBLEM
...AND NOBODY SEES IT!
15
© 2015 Actelion Pharmaceuticals Ltd
18 Jun 2015
Life Science Forum Basel 2015
ACTELION’S PRODUCT IS KNOWLEDGE
WAYS TO PRODUCE KNOWLEDGE
hypothesis
tools
experiments
SPIRIT
results
knowledge
production
from existing
information
systemic view
information
knowledge
product
revenue
16
© 2015 Actelion Pharmaceuticals Ltd
experiment
driven
knowledge
production
ACTELION’S PRODUCT IS KNOWLEDGE
WAYS TO PRODUCE KNOWLEDGE
patient space
disease space
genome
proteome
metabolome
activity space
chemical space
Edwards S W , Preston R J
Toxicol. Sci. 2008;106:312-318
17
© 2015 Actelion Pharmaceuticals Ltd
ACTELION’S
DRUG DISCOVERY LIMS
2nd Generation - The era of translational medicine
18
© 2015 Actelion Pharmaceuticals Ltd
18 Jun 2015
Life Science Forum Basel 2015
HOW TO MANAGE LIFE SCIENCE DATA
TACKLING THE PROBLEMS:
1.
The objects of these investigations are not
chemical structures, but:
animals, humans, organs, tissues, cells - alive and
in the form of preparations; proteins, genes, pathways, complex reagents - more or les defined.
2.
The variables of these investigations are
extremely diverse:
marker occurrence, distribution, concentration;
structure, shape, functional state; symptoms,
behaviour, feeling...
3.
These investigations do not uncover an inherent
property of an entity, but:
Context is everything!
19
© 2015 Actelion Pharmaceuticals Ltd
18 Jun 2015
Life Science Forum Basel 2015
SPIRIT
BASIC ELEMENTS...
result
sample
location
20
© 2015 Actelion Pharmaceuticals Ltd
18 Jun 2015
Life Science Forum Basel 2015
SPIRIT
... IN CONTEXT
treatments
sample
measurements
samplings
results
sample 1
samples
result
group A
sample 2
sample 3
study
sample 4
group B
sample 5
sample 6
timepoints t0
21
© 2015 Actelion Pharmaceuticals Ltd
18 Jun 2015
measurements
t1
t2
Life Science Forum Basel 2015
t3
t4
SPIRIT
NOT JUST A SOFTWARE
Main SPIRIT application
© 2015 Actelion Pharmaceuticals Ltd
18 Jun 2015
Life Science Forum Basel 2015
label
printers
22
balances
database
schema
role-specific .
applications .
and tablet apps .
SPIRIT
EXPERIENCE TO BE PART OF A COLLABORATIVE WORKFLOW
23
© 2015 Actelion Pharmaceuticals Ltd
18 Jun 2015
Life Science Forum Basel 2015
SPIRIT
WHAT EVERYONE WANTS TO SEE: RESULTS!
24
© 2015 Actelion Pharmaceuticals Ltd
18 Jun 2015
Life Science Forum Basel 2015
PROBLEM SOLVED?
WELL, NOT QUITE...
 Integration with clinical data
 Combining internal and external data
25
© 2015 Actelion Pharmaceuticals Ltd
18 Jun 2015
Life Science Forum Basel 2015
REACHING OUT
SPIRIT in Academia
26
© 2015 Actelion Pharmaceuticals Ltd
18 Jun 2015
Life Science Forum Basel 2015
REACHING OUT
REQUEST FROM A HOSPITAL RESEARCH LAB
 Large and increasing number of samples
from an ongoing patient cohort
 Large and increasing amount of linked
clinical and experimental patient data sets
 MS Excel sample inventory and data storage
–
risk of inadvertent data loss/corruption
–
sub-optimal data exploration possibility
pictures for illustration only, taken at Actelion
27
© 2015 Actelion Pharmaceuticals Ltd
18 Jun 2015
Life Science Forum Basel 2015
REACHING OUT
SPIRIT FOR NON-COMMERCIAL USE BY ACADEMIA
 We had a solution, and an interest to gain experience handling genetic data
 2012: SPIRIT free license to University Hospital Basel, Department of
Biomedicine
–
enabled portability (free database, scalable host/server config, web-start)
–
voluntary support (process analysis, configuration proposal, training)
–
continuous voluntary development
 2014: License extended to University of Basel
28
–
improved portability
–
60-page manual
© 2015 Actelion Pharmaceuticals Ltd
18 Jun 2015
Life Science Forum Basel 2015
REACHING OUT
SPIRIT FOR NON-COMMERCIAL USE BY ACADEMIA
 Experiences:
29
–
initial problem solved by SPIRIT, fully accepted in the lab
–
Prof. originally sceptical and disinterested, worried about data safety (!)
–
other groups interested but shy own resource contribution
–
suspicion because for free
–
most frequent worry (!): how to keep “my” data private?
© 2015 Actelion Pharmaceuticals Ltd
18 Jun 2015
Life Science Forum Basel 2015
THE PROBLEM IS COMMON
30
© 2015 Actelion Pharmaceuticals Ltd
18 Jun 2015
Life Science Forum Basel 2015
THE PROBLEM IS COMMON
AND NOT YET EFFICIENTLY TACKLED
 Pharma Industry:
–
major topic at all levels, continuous struggle
–
internal solutions and commercial solutions
–
lack of standards and compatibility causes costs, but also business cases
 Academia (eg, SiLA Consortium discussion with Biomedical Automation
Technologies and Light Microscopy & Screening Center, ETH Zürich, in 2013):
31
–
ETHZ has no institution-wide LIMS and Electronic Lab Journal
–
recognized as a serious problem, but not yet systematically tackled
© 2015 Actelion Pharmaceuticals Ltd
18 Jun 2015
Life Science Forum Basel 2015
PROPOSAL
32
© 2015 Actelion Pharmaceuticals Ltd
18 Jun 2015
Life Science Forum Basel 2015
PROPOSAL
THE SCIENCE OF SCIENCE
 Create a research group or institute to
1. investigate how life science research happens
2. identify, describe, and publish fundamental issues
3. develop, test, and publish concrete solutions
4. teach students, support local research teams
5. set new global standards
 Possible host institutions:
33
–
Fachhochschulen
–
ETH/EPFL
–
NIH/EMBL
© 2015 Actelion Pharmaceuticals Ltd
18 Jun 2015
Life Science Forum Basel 2015
PROPOSAL
THE SCIENCE OF SCIENCE
 Possible projects:
1. Develop a system of compatible standards for all experimental life sciences
data (eg, AnIML technique definitions for biological samples, genetic data...).
2. Provide nation-wide, open ELN/LIMS to deposit all SNF-sponsored research
data (eg, ETHZ to relaunch ELN standard project in Pistoia Alliance).
3. Investigate and improve the reproducibility of published research results.
34
© 2015 Actelion Pharmaceuticals Ltd
18 Jun 2015
Life Science Forum Basel 2015
PROPOSAL
THE SCIENCE OF SCIENCE
 Precedents
–
KNIME Open Platform
–
HELM notation of complex macromolecules
(Pistoia Alliance, adopted by NIH)
–
The WWW was invented 25 years ago at CERN
The image on the cover page of Tim Berners-Lee's
proposal for the World Wide Web in March 1989 (Image:
CERN)
35
© 2015 Actelion Pharmaceuticals Ltd
18 Jun 2015
Life Science Forum Basel 2015
ACKNOWLEDGEMENTS
•
Joël Freyss
Brilliant software engineer
•
Geoffroy Bourquin
Process analysis and re-design, training, hardware
•
Beat Steiner
Department head
•
Ronny Nienhold
Basel University Hospital
36
© 2015 Actelion Pharmaceuticals Ltd
18 Jun 2015
Life Science Forum Basel 2015
THANK YOU.
37
© 2015 Actelion Pharmaceuticals Ltd
18 Jun 2015
Life Science Forum Basel 2015