CINECA Curation-support application for care planning D5.4

This deliverable aims at designing and evaluating a curation support system to help clinicians to decide which treatments should be considered given a set of somatic/germline mutations and some particular clinical conditions (e.g. diagnosis). It builds on top of previous deliverables from WP5, in particular D5.1 [1], as well as on the services delivered by WP1-3, such as the WP1 dataset search services and WP3 content normalization services. In the use-case scenario described in D5.1, the end-user was first invited to select some datasets. User queries are then distributed across a federated Beacon network, comprising data from UKBB (EMBL-EBI), CoLaus (Switzerland), H3 (South Africa) and CHILD (Canada). Beyond that, the search pipeline now integrates subtask T5.3.2 (Scoring service to assess pathogenicity scales of variants) directly as an information displayed to the user, but also as a feature of the treatment recommendation function. The scoring and care planning services are evaluated based on various scoring functions (e.g., cohort distributions, SIFT, Polyphen, literature counts). The evaluation shows a moderate association between the pathogenetic scoring proposed by T5.3.2 and the baseline scores selected for comparison. We also report on the efficiency of the pipeline.