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http://hdl.handle.net/1942/21980
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DC Field | Value | Language |
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dc.contributor.author | PERUALILA, Nolen Joy | - |
dc.contributor.author | KASIM, Adetayo | - |
dc.contributor.author | TALLOEN, Willem | - |
dc.contributor.author | Verbist, Bie | - |
dc.contributor.author | Hinrich Ghoelmann | - |
dc.contributor.author | QSTAR Consortium | - |
dc.contributor.author | SHKEDY, Ziv | - |
dc.contributor.author | KHAMIAKOVA, Tatsiana | - |
dc.contributor.author | OTAVA, Martin | - |
dc.date.accessioned | 2016-09-09T08:28:01Z | - |
dc.date.available | 2016-09-09T08:28:01Z | - |
dc.date.issued | 2016 | - |
dc.identifier.citation | Statistical Applications in Genetics and Molecular Biology, 15 (4), p. 291-304 | - |
dc.identifier.issn | 2194-6302 | - |
dc.identifier.uri | http://hdl.handle.net/1942/21980 | - |
dc.description.abstract | The modern drug discovery process involves multiple sources of high-dimensional data. This imposes the challenge of data integration. A typical example is the integration of chemical structure (fingerprint features), phenotypic bioactivity (bioassay read-outs) data for targets of interest, and transcriptomic (gene expression) data in early drug discovery to better understand the chemical and biological mechanisms of candidate drugs, and to facilitate early detection of safety issues prior to later and expensive phases of drug development cycles. In this paper, we discuss a joint model for the transcriptomic and the phenotypic variables conditioned on the chemical structure. This modeling approach can be used to uncover, for a given set of compounds, the association between gene expression and biological activity taking into account the influence of the chemical structure of the compound on both variables. The model allows to detect genes that are associated with the bioactivity data facilitating the identification of potential genomic biomarkers for compounds efficacy. In addition, the effect of every structural feature on both genes and pIC50 and their associations can be simultaneously investigated. Two oncology projects are used to illustrate the applicability and usefulness of the joint model to integrate multi-source high-dimensional information to aid drug discovery. | - |
dc.description.sponsorship | We would like to thank Janssen Pharmaceutica NV for funding a part of the PhD project of Nolen Perualila-Tan. We would like to gratefully acknowledge the Institute for the Promotion of Innovation by Science and Technology in Flanders (IWT) for providing us with the O&O grant 100988: QSTAR - Quantitative structure transcriptional activity relationship. Ziv Shkedy and Nolen Perualila-Tan also gratefully acknowledge the support from the IAP Research Network P7/06 of the Belgian State (Belgian Science Policy). | - |
dc.language.iso | en | - |
dc.subject.other | bioactivity; biomarkers; chemical structure; joint model; transcriptomic | - |
dc.title | A joint modeling approach for uncovering associations between gene expression, bioactivity and chemical structure in early drug discovery to guide lead selection and genomic biomarker development | - |
dc.type | Journal Contribution | - |
dc.identifier.epage | 304 | - |
dc.identifier.issue | 4 | - |
dc.identifier.spage | 291 | - |
dc.identifier.volume | 15 | - |
local.bibliographicCitation.jcat | A1 | - |
local.contributor.corpauthor | QSTAR Consortium | - |
local.type.refereed | Refereed | - |
local.type.specified | Article | - |
dc.identifier.doi | 10.1515/sagmb-2014-0086 | - |
dc.identifier.isi | 000380816300002 | - |
item.validation | ecoom 2017 | - |
item.fulltext | No Fulltext | - |
item.fullcitation | PERUALILA, Nolen Joy; KASIM, Adetayo; TALLOEN, Willem; Verbist, Bie; Hinrich Ghoelmann; QSTAR Consortium; SHKEDY, Ziv; KHAMIAKOVA, Tatsiana & OTAVA, Martin (2016) A joint modeling approach for uncovering associations between gene expression, bioactivity and chemical structure in early drug discovery to guide lead selection and genomic biomarker development. In: Statistical Applications in Genetics and Molecular Biology, 15 (4), p. 291-304. | - |
item.accessRights | Closed Access | - |
item.contributor | PERUALILA, Nolen Joy | - |
item.contributor | KASIM, Adetayo | - |
item.contributor | TALLOEN, Willem | - |
item.contributor | Verbist, Bie | - |
item.contributor | Hinrich Ghoelmann | - |
item.contributor | QSTAR Consortium | - |
item.contributor | SHKEDY, Ziv | - |
item.contributor | KHAMIAKOVA, Tatsiana | - |
item.contributor | OTAVA, Martin | - |
crisitem.journal.issn | 2194-6302 | - |
crisitem.journal.eissn | 1544-6115 | - |
Appears in Collections: | Research publications |
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