The lack of high-throughput methods to analyze the adipose tissue protein composition limits our understanding of the protein networks responsible for age and diet related metabolic response. We have developed an approach using multiple-dimension liquid chromatography tandem mass spectrometry and extended multiplexing (24 biological samples) with tandem mass tags (TMT) labeling to analyze proteomes of epididymal adipose tissues isolated from mice fed either low or high fat diet for a short or a long-term, and from mice that aged on low high fat diets. The peripheral metabolic health (as measured by body weight, adiposity, plasma fasting glucose, insulin, triglycerides, total cholesterol levels, and glucose and insulin tolerance tests) deteriorated with diet and advancing age, with long-term high fat diet exposure being the worst. In response to short-term high fat diet, 43 proteins representing lipid metabolism ( AACS, ACOX1, ACLY) and red-ox pathways ( CPD2, CYP2E, SOD3) were significantly altered (FDR < 10%). Long-term high fat diet significantly altered 55 proteins associated with immune response ( IGTB2, IFIT3, LGALS1) and rennin angiotensin system ( ENPEP, CMA1, CPA3, ANPEP). Age-related changes on low fat diet significantly altered only 18 proteins representing mainly urea cycle ( OTC, ARG1, CPS1), and amino acid biosynthesis ( GMT, AKR1C6). Surprisingly, high fat diet driven age-related changes culminated with alterations in 155 proteins involving primarily the urea cycle ( ARG1, CPS1), immune response/complement activation ( C3, C4b, C8, C9, CFB, CFH, FGA), extracellular remodeling ( EFEMP1, FBN1, FBN2, LTBP4, FERMT2, ECM1, EMILIN2, ITIH3) and apoptosis ( YAP1, HIP1, NDRG1, PRKCD, MUL1) pathways. Using our adipose tissue tailored approach we have identified both age-related and high fat diet specific proteomic signatures highlighting a pronounced involvement of arginine metabolism in response to advancing age, and branched chain amino acid metabolism in early response to high fat feeding. Data are available via ProteomeXchange with identifier PXD005953.

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Background Electronic medical records (EMR) provide a unique opportunity for efficient, large-scale clinical investigation in psychiatry. However, such studies will require development of tools to define treatment outcome. Method Natural language processing (NLP) was applied to classify notes from 127 504 patients with a billing diagnosis of major depressive disorder, drawn from out-patient psychiatry practices affiliated with multiple, large New England hospitals. Classifications were compared with results using billing data (ICD-9 codes) alone and to a clinical gold standard based on chart review by a panel of senior clinicians. These cross-sectional classifications were then used to define longitudinal treatment outcomes, which were compared with a clinician-rated gold standard. Results Models incorporating NLP were superior to those relying on billing data alone for classifying current mood state (area under receiver operating characteristic curve of 0.85–0.88 v. 0.54–0.55). When these cross-sectional visits were integrated to define longitudinal outcomes and incorporate treatment data, 15% of the cohort remitted with a single antidepressant treatment, while 13% were identified as failing to remit despite at least two antidepressant trials. Non-remitting patients were more likely to be non-Caucasian (p<0.001). Conclusions The application of bioinformatics tools such as NLP should enable accurate and efficient determination of longitudinal outcomes, enabling existing EMR data to be applied to clinical research, including biomarker investigations. Continued development will be required to better address moderators of outcome such as adherence and co-morbidity.

Objective To validate the use of electronic health records (EHRs) for the diagnosis of bipolar disorder (BD) and controls. Methods EHR data were obtained from a healthcare system of more than 4.2 million patients spanning more than 20 years. Chart review by experienced clinicians was used to identify text features and coded data consistent or inconsistent with a diagnosis of BD. Natural language processing (NLP) was used to train a diagnostic algorithm with 95% specificity for classifying BD. Filtered coded data were used to derive three additional classification rules for cases and one for controls. The positive predictive value (PPV) of EHR-based BD and subphenotype diagnoses was calculated against direct semi-structured interview diagnoses by trained clinicians blind to EHR diagnosis in a sample of 190 patients. Results The PPV of NLP-defined BD was 0.85. A coded classification based on strict filtering achieved a PPV of 0.79, but BD classifications based on less stringent criteria performed less well. None of the EHR-classified controls was given a diagnosis of BD on direct interview (PPV = 1.0). For most subphenotypes, PPVs exceeded 0.80. The EHR-based classifications were used to accrue 4500 BD cases and 5000 controls for genetic analyses. Conclusions Semi-automated mining of EHRs can be used to ascertain BD cases and controls with high specificity and predictive value compared to a gold-standard diagnostic interview. EHRs provide a powerful resource for high-throughput phenotyping for genetic and clinical research.

BackgroundThere is wide agreement in the biomedical research community that research data sharing is a primary ingredient for ensuring that science is more transparent and reproducible. Publishers could play an important role in facilitating and enforcing data sharing; however, many journals have not yet implemented data sharing policies and the requirements vary widely across journals. This study set out to analyze the pervasiveness and quality of data sharing policies in the biomedical literature.MethodsThe online author’s instructions and editorial policies for 318 biomedical journals were manually reviewed to analyze the journal’s data sharing requirements and characteristics. The data sharing policies were ranked using a rubric to determine if data sharing was required, recommended, required only for omics data, or not addressed at all. The data sharing method and licensing recommendations were examined, as well any mention of reproducibility or similar concepts. The data was analyzed for patterns relating to publishing volume, Journal Impact Factor, and the publishing model (open access or subscription) of each journal.ResultsA total of 11.9% of journals analyzed explicitly stated that data sharing was required as a condition of publication. A total of 9.1% of journals required data sharing, but did not state that it would affect publication decisions. 23.3% of journals had a statement encouraging authors to share their data but did not require it. A total of 9.1% of journals mentioned data sharing indirectly, and only 14.8% addressed protein, proteomic, and/or genomic data sharing. There was no mention of data sharing in 31.8% of journals. Impact factors were significantly higher for journals with the strongest data sharing policies compared to all other data sharing criteria. Open access journals were not more likely to require data sharing than subscription journals.DiscussionOur study confirmed earlier investigations which observed that only a minority of biomedical journals require data sharing, and a significant association between higher Impact Factors and journals with a data sharing requirement. Moreover, while 65.7% of the journals in our study that required data sharing addressed the concept of reproducibility, as with earlier investigations, we found that most data sharing policies did not provide specific guidance on the practices that ensure data is maximally available and reusable.