Drug contraindications in comorbid diseases: a protein interactome perspective
<p dir="ltr">Adverse drug reactions (ADRs) are leading causes of death and drug withdrawals and frequently co-occur with comorbidities. However, systematic studies on the effects of drugs on comorbidities are lacking. Drug interactions with the cellular protein–protein interaction (P...
محفوظ في:
| المؤلف الرئيسي: | |
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| مؤلفون آخرون: | , , , |
| منشور في: |
2024
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| الموضوعات: | |
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إضافة وسم
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| _version_ | 1864513544587837440 |
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| author | Kalyani B. Karunakaran (12478431) |
| author2 | Madhavi K. Ganapathiraju (12478434) Sanjeev Jain (598431) Samir K. Brahmachari (7586024) N. Balakrishnan (2445499) |
| author2_role | author author author author |
| author_facet | Kalyani B. Karunakaran (12478431) Madhavi K. Ganapathiraju (12478434) Sanjeev Jain (598431) Samir K. Brahmachari (7586024) N. Balakrishnan (2445499) |
| author_role | author |
| dc.creator.none.fl_str_mv | Kalyani B. Karunakaran (12478431) Madhavi K. Ganapathiraju (12478434) Sanjeev Jain (598431) Samir K. Brahmachari (7586024) N. Balakrishnan (2445499) |
| dc.date.none.fl_str_mv | 2024-03-19T09:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1007/s13721-023-00440-3 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Drug_contraindications_in_comorbid_diseases_a_protein_interactome_perspective/29624678 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biomedical and clinical sciences Clinical sciences Pharmacology and pharmaceutical sciences Comorbidities Interactomes Adverse drug reactions Drug contraindications Drug target networks Protein–protein interactions |
| dc.title.none.fl_str_mv | Drug contraindications in comorbid diseases: a protein interactome perspective |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">Adverse drug reactions (ADRs) are leading causes of death and drug withdrawals and frequently co-occur with comorbidities. However, systematic studies on the effects of drugs on comorbidities are lacking. Drug interactions with the cellular protein–protein interaction (PPI) network give rise to ADRs. We selected 6 comorbid disease pairs, identified the drugs used in the treatment of the individual diseases ‘A’ and ‘B’– 44 drugs in anxiety and depression, 128 in asthma and hypertension, 48 in chronic obstructive pulmonary disease and heart failure, 58 in type 2 diabetes and obesity, 58 in Parkinson’s disease and schizophrenia, and 84 in rheumatoid arthritis and osteoporosis—and categorized them based on whether they aggravate the comorbid condition. We constructed drug target networks (DTNs) and examined their enrichment among genes in disease A/B PPI networks, expressed across 53 tissues and involved in ~ 1000 pathways. To characterize the biological features of the DTNs, we performed principal component analysis and computed the Euclidean distance between DTN component scores and feature loading values. DTNs of disease A drugs not contraindicated in B were affiliated with proteins common to A/B networks or uniquely found in the B network, similarly regulated common pathways, and disease-B specific pathways and tissues. DTNs of disease A drugs contraindicated in B were affiliated with common proteins or those uniquely found in the A network, differentially regulated common pathways, and disease A-specific pathways and tissues. Hence, DTN enrichment in pathways, tissues, and PPI networks of comorbid diseases will help identify drug contraindications in comorbidities.</p><h2>Other Information</h2><p dir="ltr">Published in: Network Modeling Analysis in Health Informatics and Bioinformatics<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1007/s13721-023-00440-3" target="_blank">https://dx.doi.org/10.1007/s13721-023-00440-3</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_c7e2fe2b550bfe5dd00930fa0e734a60 |
| identifier_str_mv | 10.1007/s13721-023-00440-3 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/29624678 |
| publishDate | 2024 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Drug contraindications in comorbid diseases: a protein interactome perspectiveKalyani B. Karunakaran (12478431)Madhavi K. Ganapathiraju (12478434)Sanjeev Jain (598431)Samir K. Brahmachari (7586024)N. Balakrishnan (2445499)Biomedical and clinical sciencesClinical sciencesPharmacology and pharmaceutical sciencesComorbiditiesInteractomesAdverse drug reactionsDrug contraindicationsDrug target networksProtein–protein interactions<p dir="ltr">Adverse drug reactions (ADRs) are leading causes of death and drug withdrawals and frequently co-occur with comorbidities. However, systematic studies on the effects of drugs on comorbidities are lacking. Drug interactions with the cellular protein–protein interaction (PPI) network give rise to ADRs. We selected 6 comorbid disease pairs, identified the drugs used in the treatment of the individual diseases ‘A’ and ‘B’– 44 drugs in anxiety and depression, 128 in asthma and hypertension, 48 in chronic obstructive pulmonary disease and heart failure, 58 in type 2 diabetes and obesity, 58 in Parkinson’s disease and schizophrenia, and 84 in rheumatoid arthritis and osteoporosis—and categorized them based on whether they aggravate the comorbid condition. We constructed drug target networks (DTNs) and examined their enrichment among genes in disease A/B PPI networks, expressed across 53 tissues and involved in ~ 1000 pathways. To characterize the biological features of the DTNs, we performed principal component analysis and computed the Euclidean distance between DTN component scores and feature loading values. DTNs of disease A drugs not contraindicated in B were affiliated with proteins common to A/B networks or uniquely found in the B network, similarly regulated common pathways, and disease-B specific pathways and tissues. DTNs of disease A drugs contraindicated in B were affiliated with common proteins or those uniquely found in the A network, differentially regulated common pathways, and disease A-specific pathways and tissues. Hence, DTN enrichment in pathways, tissues, and PPI networks of comorbid diseases will help identify drug contraindications in comorbidities.</p><h2>Other Information</h2><p dir="ltr">Published in: Network Modeling Analysis in Health Informatics and Bioinformatics<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1007/s13721-023-00440-3" target="_blank">https://dx.doi.org/10.1007/s13721-023-00440-3</a></p>2024-03-19T09:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1007/s13721-023-00440-3https://figshare.com/articles/journal_contribution/Drug_contraindications_in_comorbid_diseases_a_protein_interactome_perspective/29624678CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/296246782024-03-19T09:00:00Z |
| spellingShingle | Drug contraindications in comorbid diseases: a protein interactome perspective Kalyani B. Karunakaran (12478431) Biomedical and clinical sciences Clinical sciences Pharmacology and pharmaceutical sciences Comorbidities Interactomes Adverse drug reactions Drug contraindications Drug target networks Protein–protein interactions |
| status_str | publishedVersion |
| title | Drug contraindications in comorbid diseases: a protein interactome perspective |
| title_full | Drug contraindications in comorbid diseases: a protein interactome perspective |
| title_fullStr | Drug contraindications in comorbid diseases: a protein interactome perspective |
| title_full_unstemmed | Drug contraindications in comorbid diseases: a protein interactome perspective |
| title_short | Drug contraindications in comorbid diseases: a protein interactome perspective |
| title_sort | Drug contraindications in comorbid diseases: a protein interactome perspective |
| topic | Biomedical and clinical sciences Clinical sciences Pharmacology and pharmaceutical sciences Comorbidities Interactomes Adverse drug reactions Drug contraindications Drug target networks Protein–protein interactions |