Druggability

Filters

Druggability filters utilize traffic light logic to indicate the most crucial protein characteristics as a potential drug target

Small molecules

Indicates the accessibility of a protein by small molecules. Information about target druggability by small molecules is aggregated from several databases including Open Targets platform, ClinicalTrials.gov and Target Central Resource Database.

• Gene likely does not belong to the druggable family and there are no small molecules known to target gene's product
• Gene either belongs to the druggable family OR there are small molecules known to target the gene's product
• Gene belongs to the druggable family AND there are small molecules known to target gene's product

Antibodies

Indicates the ability to use antibodies to hit the target. Information about target druggability by antibodies is aggregated from several databases including Protein atlas, Target Central Resource Database and ClinicalTrials.gov.

• Genes encoding proteins which are not associated with cellular membrane and there is no information about targeting by antibodies
• Genes encoding either secreted or membrane-bound proteins or subject to potential targeting by antibodies
• Genes encoding secreted or membrane-bound proteins which can be targeted by antibodies

Safety

Safety of potential drug targets, considering potential harm and adverse effects. Information about target safety is aggregated from several databases including Database of Essential Genes and ClinicalTrials.gov.

• Essential genes whose products are not targeted by small molecules in clinical trials
• Genes with no specific evidence regarding potential target safety assessment
• Non-essential genes or genes whose products are targeted by small molecules in clinical trials

Novelty

Indicates the overall scientific community interest to the target, based on the volume of related publications proposed by the proprietary AI engine

• Genes extensively mentioned in the literature with more than 168 publications
• Genes with a moderate number of mentions in the literature, from 50 to 168 publications
• Genes relatively unexplored or less studied in the literature with fewer than 50 publications

Filter by tissue

This filter enables the user to fine-tune the search for potential drug targets based on mRNA or protein expression in specific tissues. Users can select one or more tissues and specify whether they want targets exclusively expressed in those tissues (set Specificity parameter to 0) or expressed in all tissues (set Specificity parameter to 1).

Information about gene and protein expression is collected from several databases including The Human Protein Atlas project and The Developmental Genotype-Tissue Expression database.

Gene sets

The "Gene Sets" filter allows users to tailor the TargetID results to include genes that are of particular interest, streamlining their exploration of potential drug targets. There are two ways to utilize the filter: either create a gene set from scratch or choose from a collection of predefined gene sets. For a more comprehensive analysis, users have the option to combine multiple gene sets either through an intersection or a union operation. Click the "+ Add Gene Set" button to open the corresponding modal window.

Users can use "New set" tab to manually specify the gene symbols for the genes they wish to include in the set. These user-defined gene sets can be saved for future use and later found on the "Custom sets" tab. This is particularly valuable when investigating drug targets associated with a particular pathway or biological function.

In addition to creating custom gene sets, PandaOmics provides access to a collection of predefined gene sets, known as "original sets." These gene sets encompass popular gene groupings such as signaling pathways ("Hedgehog signaling," "PI3K/AKT/mTOR signaling"), targets of transcription factors ("E2F targets," "MYC targets"), and genes implicated in various biological processes ("Inflammatory response," "Glycolysis," "Apoptosis").

Target families

These filters allow users to refine Target ID output by selecting genes belonging to one or multiple protein families such as ion channels, kinases, receptors, and transporters. The protein families are organized hierarchically, with some categories containing child categories for a more detailed classification. For instance, the "Receptor" family branches into child categories like "GPCR," "Immunoglobulin," and "Scavenger receptor."

Additionally, the "Target Families" filter offers a checkbox labeled "Show druggable classes only," which limits the displayed families to those that are considered druggable classes. This feature is especially valuable when users are specifically interested in exploring potential drug targets.

Structure

This filter indicates the presence of resolved crystal 3D structure for the gene product.

Development level

• Tclin
  Genes, whose products are targeted by approved drugs with known mechanism of action.

• Tchem
  Genes, whose products can specifically be targeted with small molecules better than the following bioactivity cutoff values: 30 nM for kinases, 100 nM for GPCRs and nuclear receptors, 10 μM for ion channels, and 1 μM for other target classes.

• Tbio
  Genes which are annotated with a Gene Ontology Molecular Function or Biological Process with an Experimental Evidence code, or targets with confirmed OMIM phenotype(s), or do not satisfy the Tdark criteria.

• Tdark
  Genes, whose products have been described at the sequence level and have very few associated studies: no information is available regarding drug or small molecule activities, no OMIM and GO terms matching Tbio criteria. At least two of the following conditions should be met:

1. PubMed text-mining score less than 5 in DISEASES database
2. Three or less GeneRIFs in NCBI Gene database
3. Fifty or less antibodies according to Antibodypedia resource.