# Target Prioritisation The new [target prioritisation page](https://platform.opentargets.org/disease/EFO_0005774/associations?table=prioritisations) can be accessed by clicking onto the **Target prioritisation factors** tab from the Associations on the Fly page when searching for targets associated with a disease or phenotype. The view focuses on displaying target-specific properties in a disease agnostic way, which have been aggregated into four main sections—**Precedence, Tractability, Doability, Safety—**and individually scored by the Open Targets team. A "traffic light" system has been designed to visually inform on target prioritisation, with the aim to facilitate target recommendations. Using a colour scale, green indicates potentially positive attributes and red indicates potentially negative attributes, providing information to help users assess the targets for further prioritisation or deprioritisation, respectively. ## Precedence section ### Target in clinic **Definition:** Gene is targeted by available drugs in any clinical stage for any indication. **Source of Data:** Drugs and Clinical Precedence for a Target ([Open Targets](https://platform-docs.opentargets.org/target/drugs)) **Scoring:** Maximum harmonised clinical stage score across all drugs acting on the target, independently of the indication. Scores follow the same scale as the [Clinical Precedence Evidence](https://platform-docs.opentargets.org/evidence#clinical-precedence) dataset, ranging from 0.01 (Preclinical or Unknown) to 1.0 (Approval, Phase IV, or Withdrawal). {% hint style="info" %} For a full description of the **clinical stage categories** and their ranking, see [Clinical stage categories](https://platform-docs.opentargets.org/drug/clinical-report#clinical-stage-categories) in the Clinical Report page. {% endhint %} ## Tractability section ### Membrane Protein **Definition:** Target is annotated to be located in the cell membrane. **Source of Data:** Platform Subcellular location widget \[HPA ([Human Protein Atlas](https://www.proteinatlas.org/)) and [UniProt](https://www.uniprot.org/)] **Scoring:** * 1 = Protein target is located (at least) in the cell or plasma membrane. * 0 = Protein target is not located in the cell membrane but some location information is accessible. * NA = No location information available. ### Secreted protein **Definition:** Target is secreted or predicted to be secreted. **Source of Data:** Platform Subcellular location widget \[HPA ([Human Protein Atlas](https://www.proteinatlas.org/)) and [UniProt](https://www.uniprot.org/)] **Scoring:** * 1 = Protein target is (at least) secreted or predicted to be secreted. * 0 = Not secreted but with location information. * NA = No location information available. {% hint style="info" %} Note: When contradictions between HPA (Human Protein Atlas) and UniProt exist (i.e. target is secreted according to HPA but in membrane according to UniProt), the information from HPA is taken. {% endhint %} ### Ligand binder **Definition:** Target binds at least one High-Quality Ligand according to ChEMBL tractability bucket. **Source of Data:** Platform tractability widget ([Open Targets tractability](https://platform-docs.opentargets.org/target/tractability)) **Scoring:** * 1 = Target has a high-quality ligand reported. * 0 = Target does not have high-quality ligand reported. * NA = No information available. ### Small molecule binder **Definition:** Target has been co-crystallised with a small molecule, reported in the Protein Data Bank. **Source of Data:** Platform tractability widget ([Open Targets tractability](https://platform-docs.opentargets.org/target/tractability)) **Scoring:** * 1 = Target has a small molecule reported. * 0 = Target does not have a small molecule reported. * NA = No information available. ### Predicted pockets **Definition:** Target has a [DrugEBIlity](https://chembl.blogspot.com/2010/10/drugebility-structure-based-component.html) score equal or above 0.7, which is predictive of harbouring a high-quality pocket. **Source of Data:** Platform tractability widget ([Open Targets tractability](https://platform-docs.opentargets.org/target/tractability)) **Scoring:** * 1 = Target contains a high-quality predicted pocket. * 0 = Target does not have a high-quality predicted pocket. * NA= No information available. ## Doability section > Models, tools and/or reagents that allow target assessment in preclinical settings to enable exploration of a given target ### Mouse ortholog identity **Definition:** Mouse orthologs maximum identity percentage. A mouse harbouring an ortholog for the target of interest could be useful for *in vivo* assaying. **Source of Data:** Platform comparative genomics widget ([Ensembl Compara](https://www.ensembl.org/info/docs/api/compara/index.html)) **Scoring:** From 0 to 1 are linearly scored those targets with at least one ortholog in mice harbouring at least 80% with the target. * 1 = There is at least one gene in mice that contains a sequence with a 100% of identity with the target. * 0 = There are no genes in mice containing a sequence with at least 80% of identity with the target. * NA = No ortholog information. {% hint style="info" %} Note: Here we consider mouse orthologs and display the "query percentage identity" (percentage of the human target sequence that matches to the mouse gene) when there is an 80% identity or more. In the cases of targets with more than one ortholog, we take the one with the maximum query % ID. {% endhint %} ### Chemical probes **Definition:** Target has high quality chemical probes. > [Chemical probes](https://platform-docs.opentargets.org/target/chemical-probes-and-teps#chemical-probes) are small molecules acting as chemical modulators, binding reversibly to the target. **Source of Data:** Platform Chemical probes widget ([Probes & Drugs](https://www.probes-drugs.org/home/)) **Scoring:** * 1 = Target has high-quality chemical probes. * 0 = Target does not have high-quality chemical probes. * NA = No information available. ## Safety section ### Genetic constraint **Definition:** Genes that are important for human physiology are seen to be depleted of deleterious variants. The Genome Aggregation Database ([gnomAD](https://gnomad.broadinstitute.org/)) has developed a continuous measurement of intolerance to loss of function (LoF) variants per gene, based on observed/expected LoF variant analysis. As recommended by gnomAD and implemented in the Open Targets platform, the rank of genes regarding their loss-of-function observed/expected upper bound fraction (LOEUF) metric is used ([LOEUF score](https://gnomad.broadinstitute.org/help/constraint#loeuf)). **Source of Data:** Platform genetic constraint widget ([gnomAD](https://gnomad.broadinstitute.org/)) **Scoring:** A score from -1 to 1 is given to genes depending on their LOEUF metric rank, being -1 the least tolerant to LoF variation and 1 the most tolerant. ### Mouse models **Definition:** The international database Mouse Genome Informatics contains information about reported phenotypes when a gene is knocked-out in this animal model. These phenotypes are categorised in multiple phenotype classes, using an organ/system classification. We retrieve this information (available in our platform) and score the phenotypes classes regarding their severity (from 0 to -1). After aggregating all phenotypes with their scores according to the phenotype class they belong to, we use the harmonic sum to build a continuous score, which is normalised from 0 to -1. **Source of Data:** Platform mouse phenotypes widget (Mouse Phenotypes, feeded from [MGI](https://www.informatics.jax.org/), a reference database for mice knockouts) **Scoring:** * Below 0 to -1 = When the target has been knocked-out in mice there were multiple and severe phenotypes reported, with a score higher than the first quartile. * 0 = Either the target has non-severe phenotypes reported or is in the first quartile of the normalised score. * NA = No information available. {% hint style="info" %} Note: Below you can find how we scored the mouse phenotype classes (-1 being the "most severe" and 0 "non relevant" phenotypes {% endhint %}
idPhenotype Classscore
MP:0005370liver/biliary system phenotype-1
MP:0005385cardiovascular system phenotype-1
MP:0010768mortality/aging-1
MP:0003631nervous system phenotype-0.75
MP:0005388respiratory system phenotype-0.75
MP:0005367renal/urinary system phenotype-0.75
MP:0005376homeostasis/metabolism phenotype-0.75
MP:0005386behavior/neurological phenotype-0.75
MP:0005381digestive/alimentary phenotype-0.5
MP:0005379endocrine/exocrine gland phenotype-0.5
MP:0005382craniofacial phenotype-0.5
MP:0005377hearing/vestibular/ear phenotype-0.5
MP:0005384cellular phenotype-0.5
MP:0005380embryo phenotype-0.5
MP:0005394taste/olfaction phenotype-0.5
MP:0002006neoplasm-0.5
MP:0005375adipose tissue phenotype-0.5
MP:0005389reproductive system phenotype-0.5
MP:0005397hematopoietic system phenotype-0.5
MP:0005387immune system phenotype-0.5
MP:0005391vision/eye phenotype-0.5
MP:0005390skeleton phenotype-0.5
MP:0005369muscle phenotype-0.25
MP:0001186pigmentation phenotype-0.25
MP:0005378growth/size/body region phenotype-0.25
MP:0005371limbs/digits/tail phenotype-0.25
MP:0010771integument phenotype-0.25
MP:0002873normal phenotype0
### Gene essentiality **Definition:** This target prioritisation feature flags common essential genes suggested by the aggregate analysis of a large number of cell lines across numerous cancer types. [DepMap](https://depmap.org/portal/) assigns common essential status to a gene by gene effect rank in the 90th percentile least dependent line. The emphasis is on the consistency rather than strength of the dependency. **Source of Data:** Gene essentiality (`CRISPRInferredCommonEssentials.csv`) is sourced from the [DepMap Portal](https://depmap.org/portal/). **Scoring:** * -1 = Target reported as essential * 0 = Target not reported as essential * NA = No information available ### **Known safety events** **Definition:** Target is associated with curated adverse events. **Source of Data:** Safety liability data from Platform safety widget ([Open Targets Safety](https://platform-docs.opentargets.org/target/safety)) and Open Targets downstream analysis of toxicity datasets from [ClinPGx](https://www.clinpgx.org/). **Scoring:** * -1 = The target has at least one adverse event. * NA = No information available. ### **Cancer driver gene** **Definition:** Target is classified as an oncogene and/or tumour suppressor gene. **Source of Data:** Platform Cancer Hallmarks widget ([COSMIC](https://cancer.sanger.ac.uk/census)) **Scoring:** We use the attribute information from the cancer hallmarks, in the target profile. Here, targets considered as "cancer driver genes" are flagged as tumour suppressor, oncogene, or both * -1 = Target is catalogued as driver gene (tumour suppressor, oncogene or both). * NA = No information available. ### **Paralogues** **Definition:** Paralogue maximum identity percentage. **Source of Data:** Platform comparative genomics widget ([Ensembl Compara](https://www.ensembl.org/info/docs/api/compara/index.html)) **Scoring:** * Below 0 to -1 are linearly scored those targets with at least one paralogue in human harbouring at least 60% of identity with the target. * 0 = Those targets with paralogues harbouring less than 60% of identity. * NA = No information available about paralogues for that target. ### Tissue specificity **Definition:** HPA assessment on tissue-specific target expression. **Source of Data:** Platform baseline expression widget ([ExpressionAtlas](https://www.ebi.ac.uk/gxa/home), [HPA](https://www.proteinatlas.org/) and [GTEx](https://www.gtexportal.org/home/)). We used the assessment for every target from the RNA expression data from the public version of Human Protein Atlas (proteinAtlasTissue) **Scoring:**
Tissue specificity HPA assessmentScore
Tissue enriched >=4 fold higher mRNA in a given tissue compared to any other1
Group enriched >=4 fold higher average mRNA in 2-5 tissue compared to any other0.75
Tissue enhanced >=4 fold higher mRNA level in a given tissue compared to average of all other tissues0.5
Low tissue specificity-1
Not detectedNA
### Tissue **distribution** **Definition:** HPA assessment on any detectable baseline expression for the target across tissues. **Source of Data:** Platform baseline expression widget ([Expression Atlas](https://www.ebi.ac.uk/gxa/home), [HPA](https://www.proteinatlas.org/) and [GTEx](https://www.gtexportal.org/home/)). We used the assessment for every target from the RNA expression data from the public version of [Human Protein Atlas](https://www.proteinatlas.org/humanproteome/tissue). **Scoring:**
Tissue distribution HPA assessmentScore
Detected in single detected in a single tissue1
Detected in some detected in more than one but less than 1/3 of tissues0.5
Detected in many detected in at least 1/3 but not all tissues0
Detected in all-1
Not detectedNA