OCDB - Documentation

OCDB: the first overall database collecting genes, miRNAs and drugs for Obsessive-Compulsive Disorder

Documentation

OCDB: the first overall database collecting genes, miRNAs and drugs for Obsessive-Compulsive Disorder

Obsessive-compulsive disorder (OCD) is a psychiatric condition characterized by intrusive and unwilling thoughts (obsessions) which give rise to anxiety. The World Health Organization ranks OCD as 1 of 10 most disabling medical conditions worldwide. The OCD is a pathology, among all anxiety disorders, for which it has been demonstrated a hereditary component. Nevertheless, there are not online resources collecting and integrating scientific discoveries and genetic evidences about OCD. We propose, OCDB, a manually curated database showing relationship between:

genes
miRNAs
drugs

As regards genes, OCDB shows nomenclature information, articles involved (focusing on experimental conditions, sample and techniques), drugs that have the gene as target, miRNAs regulating gene expression, polymorphisms, chromosomal localization of genes, pathologies in which genes can be involved and other diseases which can be associated with OCD (such as social phobia or schizophrenia in comorbidity with OCD). OCDB, for each gene, shows prediction data of miRNAs from Targetscan, Miranda, mirTarBase. In addition, OCDB, also shows prediction data of drugs (from Drugbank) for that gene. The predictions of drugs are based on DT-Hybrid (Alaimo et al, Bioinformatics) transcription factors regulations, which are also included, are taken from David and TransmiR. Moreover, a scoring function ranks the relevance of data in the OCDB context. The database is also integrated with the main online resources (PubMed, Entrez-gene HGNC, dbSNP, DrugBank, miRBase, PubChem, Kegg, Disease-ontology and EMBL-EBI ChEBI).

As regards drugs, the World Federation of Societies of Biological Psychiatry (WFSBP) published the guidelines for the pharmacological treatment of OCD. There are positive evidences for Selective serotonin reuptake inhibitors (SSRIs), Fluvoxamine, Fluoxetine, Escitalopram, Paroxetine, and Sertraline, and for one tricyclic antidepressants (TCA) Clomipramine. However, about 40% to 60% of patients do not show any improvement of symptoms. In light of this, it is needed to study and to propose alternative treatments (i.e. second-line drugs) and new drugs.

OCDB shows several drug-studies in the corresponding searching area. For each drug it shows info about the drugs, articles in which the drug is cited, gene-target of drug, the endogenous molecules on which drug acts and SNPs in the gene-target. In the endogenous molecules section, user can look at the pharmaceutical-grade, therapeutical indications, pharmacodynamics and effects of drugs on OCD obtanied from literature.

In general OCDB database is a useful resource which improves our knowledge on this pathology and to supports genome-wide analysis studies.

What is Obsessive-Compulsive Disorder (OCD)?
Everyone double checks things sometimes. For example, you might double check to make sure the stove or iron is turned off before leaving the house. But people with obsessive-compulsive disorder (OCD) feel the need to check things repeatedly, or have certain thoughts or perform routines and rituals over and over. The thoughts and rituals associated with OCD cause a huge distress in the daily life. The frequent upsetting thoughts are called obsessions. To try to control them, a person will feel an overwhelming urge to repeat certain rituals or behaviors called compulsions. People with OCD cannot control these obsessions and compulsions. Most of the time, the rituals end up controlling them. The difference is that people with OCD perform their rituals even though doing so interferes with daily life and they find the repetition distressing. Although most adults with OCD recognize their weird behavior, some of them and most of children may not realize that their behavior is out of the ordinary.

Causes
OCD sometimes runs in families, but no one knows why some people have it while others do not. Researchers have found that several parts of the brain are involved in fear and anxiety. By learning more about fear and anxiety in the brain, scientists may be able to create better treatments. Researchers are also looking for ways in which stress and environmental factors may play a role.

Signs & Symptoms
People with OCD generally:

Have repeated thoughts or images about many different things, such as fear of germs, dirt, or intruders; acts of violence; hurting loved ones; sexual acts; conflicts with religious beliefs; or being overly tidy
Do the same rituals over and over such as washing hands, locking and unlocking doors, counting, keeping unneeded items, or repeating the same steps again and again
Cannot control the unwanted thoughts and behaviors
Do not get pleasure when performing the behaviors or rituals, but get brief relief from the anxiety the thoughts cause
Spend at least 1 hour a day on the thoughts and rituals, which cause distress and get in the way of daily life

Treatments
OCD is generally treated with psychotherapy, medication, or both.

Source: National Institutes of Health

OCDB's use

Search and Advanced Search

Through the Search section, users can search by gene, miRNA and drug. In Advanced Search, users can search by article, SNP, genomic region, and drug target. A scoring method assesses the relevance to OCD of each item in OCDB.

Genes are specified by using the nomenclature of HGNC and Entrez-gene by NCBI. The nomenclature of miRNAs refers to the one used in miRBase. Drugs are inserted by their names as reported in DrugBank. Studies can be retrieved through a full text search by entering the title, the author names or year of publication. SNPs should be inserted by rs# number corresponding to the nomenclature in dbSNP. If the user searches by region, the nomenclature references to cytogenetic standards such as 9p24 or other.

In what follows we refer searched genes, miRNAs, drugs, articles, SNPs or genomic regions as items. Results are organized in the following cards:

Info: shows nomenclature information, it links to web-resources and allows to download a full card of the searched item. If the item is an article, it shows details of the publication (i.e. title, author names and so on) together with a link to PubMed, and the experiment details.
Articles: shows references to articles mentioning the item (focusing on experimental conditions, sample, software and techniques) and the pmid linked to PubMed.
Genes: shows the genes which are targets of the searched miRNA or drug, containing SNP, or genes in the searched chromosomal region. It reports the link to HGNC, gene alias, encodes, role of gene (if the gene is retrieved from articles or if the gene is validated and/or predicted miRNA's target).
miRNAs: shows the miRNA-name linked to miRBase, the effect of the miRNA on the item as well as a short description. If the item is a gene it is reported the prediction of miRNAs targeting such a gene made by TargetScan, miRanda, and mirTarBase.
Drugs: if the item is a gene, it shows drugs, linked to DrugBank, that have the gene as a target. It also reports the gene-name linked to Entrez-gene by NCBI, endogenous molecules involved and the action that the drug has on the target. There is also information about the pharmaceutical category, therapeutical indications, pharmacodynamics, pharmacological action and eventually the effects of drug on OCD extracted from the indexed articles. In addition, OCDB shows validated and prediction targets of drugs from DrugBank for that gene. The predictions are computed by the DT-Hybrid algorithm. In all other cases, this section reports details on drugs (if any) that in literature have been associated with the searched item.
SNPs: shows the SNPs in the item if present. The SNP-name is linked to dbSNP, gene-name is linked to Entrez-gene card and pmid is linked to PubMed. If there are miRNAs containing such SNP are also reported.
Regions: shows the chromosomal location of the item or targeting the item or cited in the articles.
Pathologies: shows pathologies in which the item is involved associated with OCD (such as social phobia or schizophrenia in comorbidity with OCD), reported in literature.
Transciption factors: by using DAVID, we have obtained transcription factors related to our gene set. For miRNAs, we retrieved from TransmiR the genes-miRNAs regulations.
Pathways: gives the list of pathways in which genes ente

Note that, the card corresponding to the item is not shown in the result. For example, the search by a gene does not contain in the result page the card Genes. When the item is a drug the result contains also the card "Endogenous molecules" showing the endogenous molecules and genes on which the drug may have effect. The effect is specified in "action". Users can visualize all details and relative relations with genetic elements present in the database of each item reported in the results cards by clicking "see more". By doing this, users automatically get the result of a search performed with that item. This is useful to navigate inside the database and connect information.

Browse
This interface allows to list all genes, drugs, miRNAs, studies, SNPs, and regions. The list of items with a brief description of the role of the item in the disease is returned. By clicking on "see more", users can visualize details and relative relations with genetic elements present in OCDB.
Moreover, a scoring function ranks the relevance of data in the OCDB context. The ratio behind this ranking is that OCDB does not highlight the biological importance of the item itself or the research involving it; but it weights how in our manually curated resource the item is specifically associated to OCD and to close other related pathologies, and as much information about this item and its “neighbours” (i.e. its relations) can be extracted from OCDB. Consequently, the articles are not classified but instead the items they contain. Finally, the scores are also presented as classes according to the quartile they belong; the quartiles are represented by col-ors and numbers (red-1, yellow-2, green-3, light blue-4).

License

Copyright (c) 2016 by Rosalba Giugno

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