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PregOMICS-Leveraging systems biology and bioinformatics for drug repurposing in maternal-child health.

ABSTRACT: Obstetric diseases remain underserved and understudied. Drug repurposing-utilization of a drug whose use is accepted in one condition for a different condition-could represent a rapid and low-cost way to identify new therapies that are known to be safe. In diseases of pregnancy, the known safety profile is a strong additional incentive. We describe the techniques and steps used in the use of 'omics data for drug repurposing. We illustrate these techniques using case studies of published drug repurposing projects. We provide a set of available databases with low barriers to entry which investigators can use to perform their own projects. The promise of 'omics techniques is unbiased screening, either of all drug targets or of all patients using particular drugs to find which are likely to alter disease risk or progression. However, we caution that reproducibility across the underlying studies, and thus the drugs suggested for repurposing, can be poor. We suggest that improved nosology, for example correlating patient clinical conditions with placental pathology, could yield more robust associations. We conclude that 'omics-driven drug repurposing represents a potential fruitful path to discover new, safe treatments of obstetric diseases.

SUBMITTER: Goldstein JA

PROVIDER: S-EPMC6105384 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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PregOMICS-Leveraging systems biology and bioinformatics for drug repurposing in maternal-child health.

Goldstein Jeffery A JA Bastarache Lisa A LA Denny Joshua C JC Pulley Jill M JM Aronoff David M DM

American journal of reproductive immunology (New York, N.Y. : 1989) 20180504 2

Obstetric diseases remain underserved and understudied. Drug repurposing-utilization of a drug whose use is accepted in one condition for a different condition-could represent a rapid and low-cost way to identify new therapies that are known to be safe. In diseases of pregnancy, the known safety profile is a strong additional incentive. We describe the techniques and steps used in the use of 'omics data for drug repurposing. We illustrate these techniques using case studies of published drug rep ...[more]

PMID: 29726581

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Project description:Although neuropsychiatric (NP) disorders are among the top causes of disability worldwide with enormous financial costs, they can still be viewed as part of the most complex disorders that are of unknown etiology and incomprehensible pathophysiology. The complexity of NP disorders arises from their etiologic heterogeneity and the concurrent influence of environmental and genetic factors. In addition, the absence of rigid boundaries between the normal and diseased state, the remarkable overlap of symptoms among conditions, the high inter-individual and inter-population variations, and the absence of discriminative molecular and/or imaging biomarkers for these diseases makes difficult an accurate diagnosis. Along with the complexity of NP disorders, the practice of psychiatry suffers from a "top-down" method that relied on symptom checklists. Although checklist diagnoses cost less in terms of time and money, they are less accurate than a comprehensive assessment. Thus, reliable and objective diagnostic tools such as biomarkers are needed that can detect and discriminate among NP disorders. The real promise in understanding the pathophysiology of NP disorders lies in bringing back psychiatry to its biological basis in a systemic approach which is needed given the NP disorders' complexity to understand their normal functioning and response to perturbation. This approach is implemented in the systems biology discipline that enables the discovery of disease-specific NP biomarkers for diagnosis and therapeutics. Systems biology involves the use of sophisticated computer software "omics"-based discovery tools and advanced performance computational techniques in order to understand the behavior of biological systems and identify diagnostic and prognostic biomarkers specific for NP disorders together with new targets of therapeutics. In this review, we try to shed light on the need of systems biology, bioinformatics, and biomarkers in neuropsychiatry, and illustrate how the knowledge gained through these methodologies can be translated into clinical use providing clinicians with improved ability to diagnose, manage, and treat NP patients.

Project description:Importance: There is an unprecedented need to rapidly identify safe and effective treatments for the novel coronavirus disease 2019 (COVID-19). Objective: To systematically investigate if any of the available drugs in Electronic Health Record (EHR), including prescription drugs and dietary supplements, can be repurposed as potential treatment for COVID-19. Design, Setting, and Participants: Based on a retrospective cohort analysis of EHR data, drug-wide association studies (DrugWAS) were performed on COVID-19 patients at Vanderbilt University Medical Center (VUMC). For each drug study, multivariable logistic regression with overlap weighting using propensity score was applied to estimate the effect of drug exposure on COVID-19 disease outcomes. Exposures: Patient exposure to a drug during 1-year prior to the pandemic and COVID-19 diagnosis was chosen as exposure of interest. Natural language processing was employed to extract drug information from clinical notes, in addition to the prescription drug data available in structured format. Main Outcomes and Measures: All-cause of death was selected as primary outcome. Hospitalization, admission to the intensive care unit (ICU), and need for mechanical ventilation were identified as secondary outcomes. Results: The study included 7,768 COVID-19 patients, of which 509 (6.55%) were hospitalized, 82 (1.06%) were admitted to ICU, 64 (0.82%) received mechanical ventilation, and 90 (1.16%) died. Overall, 15 drugs were significantly associated with decreased COVID-19 severity. Previous exposure to either Streptococcus pneumoniae vaccines (adjusted odds ratio [OR], 0.38; 95% CI, 0.14-0.98), diphtheria toxoid vaccine (OR, 0.39; 95% CI, 0.15-0.98), and tetanus toxoid vaccine (OR, 0.39; 95% CI, 0.15-0.98) were significantly associated with a decreased risk of death (primary outcome). Secondary analyses identified several other significant associations showing lower risk for COVID-19 outcomes: 2 vaccines (acellular pertussis, Streptococcus pneumoniae), 3 dietary supplements (turmeric extract, flaxseed extract, omega-3 fatty acids), methylprednisolone acetate, pseudoephedrine, ethinyl estradiol, estradiol, ibuprofen, and fluticasone. Conclusions and Relevance: This cohort study leveraged EHR data to identify a list of drugs that could be repurposed to improve COVID-19 outcomes. Further randomized clinical trials are needed to investigate the efficacy of the proposed drugs.

Dataset Information

PregOMICS-Leveraging systems biology and bioinformatics for drug repurposing in maternal-child health.

Publications

PregOMICS-Leveraging systems biology and bioinformatics for drug repurposing in maternal-child health.

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