Phenotype Advanced Form

You can use the advanced form to further refine your phenotype filtering

Note that you cannot use both the simplified form above and the advanced form below at the same time. This will produce unpredictable results! You have been warned!

To annotate phenotypes and/or validation experiments, we are using a phenotype syntax composed of terms derived from a number of controlled vocabularies (i.e. ontologies, e.g. GO, PATO, ECO). The syntax we are using is similar in spirit to the Pheno-syntax format described by Chris Mungall, although we have not attempted to formally comply with the pheno-syntax grammar.

The syntax consists of a collection of tag-values. Tags are i) the phenotypic quality or attribute (Q), ii) the entity bearing the phenotype (B), iii) an anatomy term that describes where the phenotype occurs (A) — not relevant for unicellular organisms, and iv) a term describing the timing during which the phenotype occurs (T) – usually a developmental stage.

As an example, the way to describe "slow growth in bloodstream forms" using this syntax is:

• Phenotypic Quality (Q) = slow
• Affected entity (B) = growth
• During (T) = bloodstream form
• Where (A) = whole organism

In this case the affected entity is growth and the way in which the growth is affected is described by the Q term (slow in this case), and this phenotype occurs in the whole organism.

The form below gives you access to search for targets using any of the terms we have used to annotate them. Do note that only a few combinations of Q, B, A, and T terms are represented in the db, even though you can search for all of them!

The druggability index query lets you restrict your search based on a druggability measure.

The Network Druggability Score (NDS) is a TDR Targets proxy for druggability, calculated using Berenstein et al (2017) approach for drug repurposing. The NDS score is a float number, ranging from 0 to 1, that represents the degree of connections between a given protein and other proteins which are known druggable targets: the higher the degree, the higher the NDS. We have stratified druggability into groups (or Tiers), that range from 1 to 5, being 1 the least likely to be druggable, and 5 the most. Tiers are assigned according to their corrsponding NDS, and the number of thresholds this NDS is above of:

• DG 1: Targets with an NDS between zero and the noise threshold, which is calculated as ten times the mean value of the lowest 25% of the values.
• DG 2: Targets with an NDS between the noise and the Youden Cutoff threshold (Y), which is calculated from the Youden's J index obtained during ROC validations (when possible; or derived from the closest species Youden's J index available).
• DG 3-5: Targets with an NDS 1, 10 and 100 times this value greater than Youden Cuttoff threshold.

It is important to address that whether an NDS is "high" or "low" is species dependant (e.g: Highest NDS in Trypanosoma cruzi is 0.24, for Tier 5 TcCLB.509153.90 target), which implies that NDS values are only comparable within a given species.

It is also important to note that a known druggable target is almost guaranteed to be a top tiered (>3) target, but a low tiered target is not necessarily a non-druggable target

Associated compounds: associations between genes and chemical compounds are derived from a number of sources. In each case the association between a gene and a compound has been done by different methods, and thus the reliability and/or the relevance of the association is different for each source. You may use this to filter targets based on:

• Manual curation (more reliable, more relevant)
• Similarity or orthology extrapolated compounds from gene A based on its similarity to a gene B for which there are known compounds.
• Network Derived Putative Interactions which derive from the NDS calculations (described above) but are done exclussively for orphan compounds (those that are active against a given pathogen but whose molecular target is yet unknown).