ArticlePharmaceuticals (Basel, Switzerland)2022
Proteomic Network Analysis of Bronchoalveolar Lavage Fluid in Ex-Smokers to Discover Implicated Protein Targets and Novel Drug Treatments for Chronic Obstructive Pulmonary Disease.
Article in Pharmaceuticals (Basel, Switzerland), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 14 citations in OpenAlex.
- Evaluation of common protein biomarkers involved in the pathogenesis of respiratory diseases with proteomic methods: A systematic review.Immunity, inflammation and disease · 2023Pooled it
- Combining cutting edge computational and experimental methods for targeting KRAS mutations in non-small cell lung cancer.Expert opinion on drug discovery · 2026Review
- Clinical peptidomics for respiratory diseases: matrices, workflows, and translation towards treatable traits, with a focus on COPD.Clinical proteomics · 2026Review
- Multiscale analysis and optimal glioma therapeutic candidate discovery using the CANDO platform.Journal of cheminformatics · 2026Article
- Uncovering novel therapeutics for schizophrenia: a multitarget approach using the CANDO platform.bioRxiv : the preprint server for biology · 2026Article
- Strategies for robust, accurate, and generalizable benchmarking of drug discovery platforms.Bioinformatics (Oxford, England) · 2025Article
- Strategies for robust, accurate, and generalizable benchmarking of drug discovery platforms.bioRxiv : the preprint server for biology · 2025Article
- A quantitative proteomic approach to evaluate the efficacy of carnosine in a murine model of chronic obstructive pulmonary disease (COPD).Redox biology · 2024Article
- Proteomic networks and related genetic variants associated with smoking and chronic obstructive pulmonary disease.BMC genomics · 2024Article
- Pneumonic Injury and Repair: A Synopsis.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Multiscale Analysis and Validation of Effective Drug Combinations Targeting Driver KRAS Mutations in Non-Small Cell Lung Cancer.International journal of molecular sciences · 2023Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Bronchoalveolar lavage of the epithelial lining fluid (BALF) can sample the profound changes in the airway lumen milieu prevalent in chronic obstructive pulmonary disease (COPD). We compared the BALF proteome of ex-smokers with moderate COPD who are not in exacerbation status to non-smoking healthy control subjects and applied proteome-scale translational bioinformatics approaches to identify potential therapeutic protein targets and drugs that modulate these proteins for the treatment of COPD. Proteomic profiles of BALF were obtained from (1) never-smoker control subjects with normal lung function (n = 10) or (2) individuals with stable moderate (GOLD stage 2, FEV1 50−80% predicted, FEV1/FVC < 0.70) COPD who were ex-smokers for at least 1 year (n = 10). After identifying potential crucial hub proteins, drug−proteome interaction signatures were ranked by the computational analysis of novel drug opportunities (CANDO) platform for multiscale therapeutic discovery to identify potentially repurposable drugs. Subsequently, a literature-based knowledge graph was utilized to rank combinations of drugs that most likely ameliorate inflammatory processes. Proteomic network analysis demonstrated that 233 of the >1800 proteins identified in the BALF were significantly differentially expressed in COPD versus control. Functional annotation of the differentially expressed proteins was used to detail canonical pathways containing the differential expressed proteins. Topological network analysis demonstrated that four putative proteins act as central node proteins in COPD. The drugs with the most similar interaction signatures to approved COPD drugs were extracted with the CANDO platform. The drugs identified using CANDO were subsequently analyzed using a knowledge-based technique to determine an optimal two-drug combination that had the most appropriate effect on the central node proteins. Network analysis of the BALF proteome identified critical targets that have critical roles in modulating COPD pathogenesis, for which we identified several drugs that could be repurposed to treat COPD using a multiscale shotgun drug discovery approach.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.