Abstract
High-throughput screening (HTS) is the main starting point for hit identification in drug discovery programs. This has led to a rapid increase of available screening data both within pharmaceutical companies and the public domain. We have used the BioAssay Ontology (BAO) 2.0 for assay annotation within AstraZeneca to enable comparison with external HTS methods. The annotated assays have been analyzed to identify technology gaps, evaluate new methods, verify active hits, and compare compound activity between in-house and PubChem assays. As an example, the binding of a fluorescent ligand to formyl peptide receptor 1 (FPR1, involved in inflammation, for example) in an in-house HTS was measured by fluorescence intensity. In total, 155 active compounds were also tested in an external ligand binding flow cytometry assay, a method not used for in-house HTS detection. Twelve percent of the 155 compounds were found active in both assays. By the annotation of assay protocols using BAO terms, internal and external assays can easily be identified and method comparison facilitated. They can be used to evaluate the effectiveness of different assay methods, design appropriate confirmatory and counterassays, and analyze the activity of compounds for identification of technology artifacts.
| Original language | English |
|---|---|
| Pages (from-to) | 402-415 |
| Number of pages | 14 |
| Journal | Journal of Biomolecular Screening |
| Volume | 20 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 25 2015 |
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Keywords
- assay design
- BioAssay Ontology
- detection technology
- high-throughput screening
- PubChem
ASJC Scopus subject areas
- Analytical Chemistry
- Drug Discovery
- Pharmacology
- Biochemistry
- Molecular Medicine
- Biotechnology
Cite this
Using the BioAssay Ontology for analyzing high-throughput screening data. / Zander Balderud, Linda; Murray, David; Larsson, Niklas; Vempati, Uma; Schuerer, Stephan C; Bjäreland, Marcus; Engkvist, Ola.
In: Journal of Biomolecular Screening, Vol. 20, No. 3, 25.03.2015, p. 402-415.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Using the BioAssay Ontology for analyzing high-throughput screening data
AU - Zander Balderud, Linda
AU - Murray, David
AU - Larsson, Niklas
AU - Vempati, Uma
AU - Schuerer, Stephan C
AU - Bjäreland, Marcus
AU - Engkvist, Ola
PY - 2015/3/25
Y1 - 2015/3/25
N2 - High-throughput screening (HTS) is the main starting point for hit identification in drug discovery programs. This has led to a rapid increase of available screening data both within pharmaceutical companies and the public domain. We have used the BioAssay Ontology (BAO) 2.0 for assay annotation within AstraZeneca to enable comparison with external HTS methods. The annotated assays have been analyzed to identify technology gaps, evaluate new methods, verify active hits, and compare compound activity between in-house and PubChem assays. As an example, the binding of a fluorescent ligand to formyl peptide receptor 1 (FPR1, involved in inflammation, for example) in an in-house HTS was measured by fluorescence intensity. In total, 155 active compounds were also tested in an external ligand binding flow cytometry assay, a method not used for in-house HTS detection. Twelve percent of the 155 compounds were found active in both assays. By the annotation of assay protocols using BAO terms, internal and external assays can easily be identified and method comparison facilitated. They can be used to evaluate the effectiveness of different assay methods, design appropriate confirmatory and counterassays, and analyze the activity of compounds for identification of technology artifacts.
AB - High-throughput screening (HTS) is the main starting point for hit identification in drug discovery programs. This has led to a rapid increase of available screening data both within pharmaceutical companies and the public domain. We have used the BioAssay Ontology (BAO) 2.0 for assay annotation within AstraZeneca to enable comparison with external HTS methods. The annotated assays have been analyzed to identify technology gaps, evaluate new methods, verify active hits, and compare compound activity between in-house and PubChem assays. As an example, the binding of a fluorescent ligand to formyl peptide receptor 1 (FPR1, involved in inflammation, for example) in an in-house HTS was measured by fluorescence intensity. In total, 155 active compounds were also tested in an external ligand binding flow cytometry assay, a method not used for in-house HTS detection. Twelve percent of the 155 compounds were found active in both assays. By the annotation of assay protocols using BAO terms, internal and external assays can easily be identified and method comparison facilitated. They can be used to evaluate the effectiveness of different assay methods, design appropriate confirmatory and counterassays, and analyze the activity of compounds for identification of technology artifacts.
KW - assay design
KW - BioAssay Ontology
KW - detection technology
KW - high-throughput screening
KW - PubChem
UR - http://www.scopus.com/inward/record.url?scp=84923321946&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84923321946&partnerID=8YFLogxK
U2 - 10.1177/1087057114563493
DO - 10.1177/1087057114563493
M3 - Article
C2 - 25512330
AN - SCOPUS:84923321946
VL - 20
SP - 402
EP - 415
JO - Journal of Biomolecular Screening
JF - Journal of Biomolecular Screening
SN - 1087-0571
IS - 3
ER -