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Concept Modeling-based Drug Repositioning.

Patchala J, Jegga AG - AMIA Jt Summits Transl Sci Proc (2015)

Bottom Line: To test this, we constructed a probabilistic topic model based on the Unified Medical Language System (UMLS) concepts that appear in the disease and drug related abstracts in MEDLINE.The resulting probabilistic topic associations were used to measure the similarity between disease and drugs.The success of the proposed model is evaluated using a set of repositioned drugs, and comparing a drug's ranking based on its similarity to the original and new indication.

View Article: PubMed Central - PubMed

Affiliation: Department of Computer Science, University of Cincinnati, Cincinnati, Ohio, USA.

ABSTRACT
Our hypothesis is that drugs and diseases sharing similar biomedical and genomic concepts are likely to be related, and thus repositioning opportunities can be identified by ranking drugs based on the incidence of shared similar concepts with diseases and vice versa. To test this, we constructed a probabilistic topic model based on the Unified Medical Language System (UMLS) concepts that appear in the disease and drug related abstracts in MEDLINE. The resulting probabilistic topic associations were used to measure the similarity between disease and drugs. The success of the proposed model is evaluated using a set of repositioned drugs, and comparing a drug's ranking based on its similarity to the original and new indication. We then applied the model to rare disorders and compared them to all approved drugs to facilitate "systematically serendipitous" discovery of relationships between rare diseases and existing drugs, some of which could be potential repositioning candidates.

No MeSH data available.


Related in: MedlinePlus

Stacked bar chart showing the top ranked drugs for PV along with distribution of top five topic proportions
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f3-2089413: Stacked bar chart showing the top ranked drugs for PV along with distribution of top five topic proportions

Mentions: In case of the rare disease PV, topic 4 (Fig. 3) which was shared between the three top ranked drugs (pipobroman, ruxolitinib and tofacitinib) and PV are related to etiology of PV (e.g., Janus kinase 2, Primary Myelofibrosis, Myeloproliferative disease, Essential Thrombocythemia, Alleles, Signal Transduction, cytokine, Janus kinase, Thrombosis, Janus kinase 1, Janus kinase 3, Interleukin-6, etc.). Drugs ranked 4th an 5th (anagrelide and eltrombopag), interestingly are, used for thrombocytosis and thrombocytopenia and are related to PV through topic 1 (Blood Platelets, Essential Thrombocythemia, Thrombocytopenia, Thrombocytosis, Megakaryocytes, Idiopathic Thrombocytopenic Purpura, Thrombopoiesis, Thrombosis, Thrombopoietin, Thrombus, etc.) representing platelets and platelet-related concepts. Anagrelide reduces the platelet count and is reported to be beneficial in some patients and is recommended as second line-therapy in PV26.


Concept Modeling-based Drug Repositioning.

Patchala J, Jegga AG - AMIA Jt Summits Transl Sci Proc (2015)

Stacked bar chart showing the top ranked drugs for PV along with distribution of top five topic proportions
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4525261&req=5

f3-2089413: Stacked bar chart showing the top ranked drugs for PV along with distribution of top five topic proportions
Mentions: In case of the rare disease PV, topic 4 (Fig. 3) which was shared between the three top ranked drugs (pipobroman, ruxolitinib and tofacitinib) and PV are related to etiology of PV (e.g., Janus kinase 2, Primary Myelofibrosis, Myeloproliferative disease, Essential Thrombocythemia, Alleles, Signal Transduction, cytokine, Janus kinase, Thrombosis, Janus kinase 1, Janus kinase 3, Interleukin-6, etc.). Drugs ranked 4th an 5th (anagrelide and eltrombopag), interestingly are, used for thrombocytosis and thrombocytopenia and are related to PV through topic 1 (Blood Platelets, Essential Thrombocythemia, Thrombocytopenia, Thrombocytosis, Megakaryocytes, Idiopathic Thrombocytopenic Purpura, Thrombopoiesis, Thrombosis, Thrombopoietin, Thrombus, etc.) representing platelets and platelet-related concepts. Anagrelide reduces the platelet count and is reported to be beneficial in some patients and is recommended as second line-therapy in PV26.

Bottom Line: To test this, we constructed a probabilistic topic model based on the Unified Medical Language System (UMLS) concepts that appear in the disease and drug related abstracts in MEDLINE.The resulting probabilistic topic associations were used to measure the similarity between disease and drugs.The success of the proposed model is evaluated using a set of repositioned drugs, and comparing a drug's ranking based on its similarity to the original and new indication.

View Article: PubMed Central - PubMed

Affiliation: Department of Computer Science, University of Cincinnati, Cincinnati, Ohio, USA.

ABSTRACT
Our hypothesis is that drugs and diseases sharing similar biomedical and genomic concepts are likely to be related, and thus repositioning opportunities can be identified by ranking drugs based on the incidence of shared similar concepts with diseases and vice versa. To test this, we constructed a probabilistic topic model based on the Unified Medical Language System (UMLS) concepts that appear in the disease and drug related abstracts in MEDLINE. The resulting probabilistic topic associations were used to measure the similarity between disease and drugs. The success of the proposed model is evaluated using a set of repositioned drugs, and comparing a drug's ranking based on its similarity to the original and new indication. We then applied the model to rare disorders and compared them to all approved drugs to facilitate "systematically serendipitous" discovery of relationships between rare diseases and existing drugs, some of which could be potential repositioning candidates.

No MeSH data available.


Related in: MedlinePlus