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Gene Ontology curation of the blood-brain barrier to improve the analysis of Alzheimer's and other neurological diseases.

ABSTRACT: The role of the blood-brain barrier (BBB) in Alzheimer's and other neurodegenerative diseases is still the subject of many studies. However, those studies using high-throughput methods have been compromised by the lack of Gene Ontology (GO) annotations describing the role of proteins in the normal function of the BBB. The GO Consortium provides a gold-standard bioinformatics resource used for analysis and interpretation of large biomedical data sets. However, the GO is also used by other research communities and, therefore, must meet a variety of demands on the breadth and depth of information that is provided. To meet the needs of the Alzheimer's research community we have focused on the GO annotation of the BBB, with over 100 transport or junctional proteins prioritized for annotation. This project has led to a substantial increase in the number of human proteins associated with BBB-relevant GO terms as well as more comprehensive annotation of these proteins in many other processes. Furthermore, data describing the microRNAs that regulate the expression of these priority proteins have also been curated. Thus, this project has increased both the breadth and depth of annotation for these prioritized BBB proteins. Database URLhttps://www.ebi.ac.uk/QuickGO/.

SUBMITTER: Saverimuttu SCC

PROVIDER: S-EPMC8546235 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Gene Ontology curation of the blood-brain barrier to improve the analysis of Alzheimer's and other neurological diseases.

Saverimuttu Shirin C C SCC Kramarz Barbara B Rodríguez-López Milagros M Garmiri Penelope P Attrill Helen H Thurlow Katherine E KE Makris Marios M de Miranda Pinheiro Sandra S Orchard Sandra S Lovering Ruth C RC

Database : the journal of biological databases and curation 20211001

The role of the blood-brain barrier (BBB) in Alzheimer's and other neurodegenerative diseases is still the subject of many studies. However, those studies using high-throughput methods have been compromised by the lack of Gene Ontology (GO) annotations describing the role of proteins in the normal function of the BBB. The GO Consortium provides a gold-standard bioinformatics resource used for analysis and interpretation of large biomedical data sets. However, the GO is also used by other researc ...[more]

PMID: 34697638

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Project description:BackgroundDisease progression and delayed neurological complications are common after aneurysmal subarachnoid hemorrhage (aSAH). We explored the potential of quantitative blood-brain barrier (BBB) imaging to predict disease progression and neurological outcome.MethodsData were collected as part of the Co-Operative Studies of Brain Injury Depolarizations (COSBID). We analyzed retrospectively, blinded and semi-automatically magnetic resonance images from 124 aSAH patients scanned at 4 time points (24-48 h, 6-8 days, 12-15 days and 6-12 months) after the initial hemorrhage. Volume of brain with apparent pathology and/or BBB dysfunction (BBBD), subarachnoid space and lateral ventricles were measured. Neurological status on admission was assessed using the World Federation of Neurosurgical Societies and Rosen-Macdonald scores. Outcome at ≥6 months was assessed using the extended Glasgow outcome scale and disease course (progressive or non-progressive based on imaging-detected loss of normal brain tissue in consecutive scans). Logistic regression was used to define biomarkers that best predict outcomes. Receiver operating characteristic analysis was performed to assess accuracy of outcome prediction models.FindingsIn the present cohort, 63% of patients had progressive and 37% non-progressive disease course. Progressive course was associated with worse outcome at ≥6 months (sensitivity of 98% and specificity of 97%). Brain volume with BBBD was significantly larger in patients with progressive course already 24-48 h after admission (2.23 (1.23-3.17) folds, median with 95%CI), and persisted at all time points. The highest probability of a BBB-disrupted voxel to become pathological was found at a distance of ≤1 cm from the brain with apparent pathology (0·284 (0·122-0·594), p < 0·001, median with 95%CI). A multivariate logistic regression model revealed power for BBBD in combination with RMS at 24-48 h in predicting outcome (ROC area under the curve = 0·829, p < 0·001).InterpretationWe suggest that early identification of BBBD may serve as a key predictive biomarker for neurological outcome in aSAH. FUND: Dr. Dreier was supported by grants from the Deutsche Forschungsgemeinschaft (DFG) (DFG DR 323/5-1 and DFG DR 323/10-1), the Bundesministerium für Bildung und Forschung (BMBF) Center for Stroke Research Berlin 01 EO 0801 and FP7 no 602150 CENTER-TBI. Dr. Friedman was supported by grants from Israel Science Foundation and Canada Institute for Health Research (CIHR). Dr. Friedman was supported by grants from European Union's Seventh Framework Program (FP7/2007-2013; grant #602102).

Dataset Information

Gene Ontology curation of the blood-brain barrier to improve the analysis of Alzheimer's and other neurological diseases.

Publications

Gene Ontology curation of the blood-brain barrier to improve the analysis of Alzheimer's and other neurological diseases.

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