Expression Search

1. Search

In the expression search tab, the user can input a list of genes using many types of ID. The page opens by default on “search by Gene Symbol” but, hovering over “Search Genes” on the top menu, the user can choose also UniProt, Entrez, RefSeq IDs.

When users input the list of genes of interest, they can:

• Verify Genes, downloading a .txt files that includes the user’s IDs present in OsteoDIP
• Check for “Available Genes”, downloading a .txt files that includes all the IDs present in OsteoDIP

A user can choose the joint (i.e. knee), the tissue (i.e. cartilage) and the Molecule Data Type (i.e. mRNA), but it is not required to proceed with the search. Moreover, the type of studies to be used can be chosen as well (DTE = Drug Treatment Effect, DvsD = Disease vs Disease, DvsN = Disease vs Normal).

If a user does not have a list of genes but one (or more) chromosomal region, they can use the “Search by cytoband” tab. OsteoDIP will be queried using all the genes located in that/those cytoband(s). It is also possible to use “Search by chromosome” to query all the genes present in that chromosome.

Clicking “Search Microarray” provides the results of the queried search.

It is also possible to perform the same search using mature microRNA IDs using the “Search microRNAs” tab.

2. Results

The resulting matrix shows, for each gene, if it was present and how it was deregulated in a study. A transparent square means the gene was not reported deregulated in the study, red and green squares mean that a gene was reported as up- or down-regulated (respectively) in a study. Blue and yellow squares mean that a gene was reported as hyper- or hypo-methylated (respectively) in a study, while a pink or brown square mean that a study reported a protective or susceptibility SNP (respectively) for that gene.

The studies, and the tables, from which the data is retrieved are listed below the matrix.

It is also possible to retrieve, for each gene listed in at least one study, details about:

• The gene chromosomal location and alternative IDs
• If the gene has been linked to a disease in DisGeNET
• If SNPedia lists a SNP associated to this gene
• If the protein is secreted, according to Human Protein Atlas or MetazSecKB
• The protein interactions that are annotated with a cartilage related tissue, according to IID
• The conservation of the protein interactions across species

It is also possible to see where the genes are located on the chromosome ideograms, search for microRNAs or Transcription Factors targeting the genes of interest (via mirDIP and Catrin, respectively), and perform pathway enrichment analysis via pathDIP.

 

If a user is not focused on a specific set of genes but rather interested in the genes more frequently deregulated in OsteoDIP, the “Search Regulated” tab can be used. In the resulting search, the matrix shows how many genes are deregulated above a user-selected threshold, and the details for each gene are the same as described above. It is also possible, after obtaining the results, to look for microRNAs that target the genes of interest, and obtain the set of all the microRNAs that target any of the genes from the original list (“union”) or the set of microRNAs that target all the genes from the original list (“overlap”).



Radiographic Biomarker

In this search tab, the user can use multiple filters to select data from papers that provide radiographic biomarkers data. To retrieve all the studies, the user can leave the filter at default.

The data can be searched and displayed or downloaded.

The resulting matrix shows, for each study, the type of comparison obtained in that study as well as the values and specific measures obtained for such comparison. Text above the matrix shows if a filter was used to select the data.

GEO Series

In this tab the user can select desired features to query a set of curated GEO (https://www.ncbi.nlm.nih.gov/geo/) datasets. Filters include the source samples, clinical and demographic features. It is also possible to query the set that for a specific Gene Symbol or probeset ID (the latter available only for microarray data).

If the user selects “Display”, then OsteoDIP will show all the GEO datasets that include the options selected in the Search page. If the user selects “Download”, the OsteoDIP will return three files per dataset selected, one including the curated clinical data and two including expression - one as provided by GEO and one RMA normalized. If the user had selected a gene/probeset, then only the expression of that gene/probeset will be returned.

If the user is interested in all the curated clinical data present in our set, then the “Clinical” tab can be used to download it.