Computational identification of disease models through cross-species phenotype comparison.

The use of standardised phenotyping screens to identify abnormal phenotypes in mouse knockouts, together with the use of ontologies to describe such phenotypic features, allows the implementation of an automated and unbiased pipeline to identify new models of disease by performing phenotype comparisons across species. Using data from the International Mouse Phenotyping Consortium (IMPC), approximately half of mouse mutants are able to mimic, at least partially, the human ortholog disease phenotypes as computed by the PhenoDigm algorithm. We found the number of phenotypic abnormalities in the mouse and the corresponding Mendelian disorder, the pleiotropy and severity of the disease, and the viability and zygosity status of the mouse knockout to be associated with the ability of mouse models to recapitulate the human disorder. An analysis of the IMPC impact on disease gene discovery through a publication-tracking system revealed that the resource has been implicated in at least 109 validated rare disease-gene associations over the last decade.

The International Mouse Phenotyping Consortium: comprehensive knockout phenotyping underpinning the study of human disease.

The International Mouse Phenotyping Consortium (IMPC; https://www.mousephenotype.org/) web portal makes available curated, integrated and analysed knockout mouse phenotyping data generated by the IMPC project consisting of 85M data points and over 95,000 statistically significant phenotype hits mapped to human diseases. The IMPC portal delivers a substantial reference dataset that supports the enrichment of various domain-specific projects and databases, as well as the wider research and clinical community, where the IMPC genotype-phenotype knowledge contributes to the molecular diagnosis of patients affected by rare disorders. Data from 9,000 mouse lines and 750 000 images provides vital resources enabling the interpretation of the ignorome, and advancing our knowledge on mammalian gene function and the mechanisms underlying phenotypes associated with human diseases. The resource is widely integrated and the lines have been used in over 4,600 publications indicating the value of the data and the materials.

The NHGRI-EBI GWAS Catalog: knowledgebase and deposition resource.

The NHGRI-EBI GWAS Catalog (www.ebi.ac.uk/gwas) is a FAIR knowledgebase providing detailed, structured, standardised and interoperable genome-wide association study (GWAS) data to >200 000 users per year from academic research, healthcare and industry. The Catalog contains variant-trait associations and supporting metadata for >45 000 published GWAS across >5000 human traits, and >40 000 full P-value summary statistics datasets. Content is curated from publications or acquired via author submission of prepublication summary statistics through a new submission portal and validation tool. GWAS data volume has vastly increased in recent years. We have updated our software to meet this scaling challenge and to enable rapid release of submitted summary statistics. The scope of the repository has expanded to include additional data types of high interest to the community, including sequencing-based GWAS, gene-based analyses and copy number variation analyses. Community outreach has increased the number of shared datasets from under-represented traits, e.g. cancer, and we continue to contribute to awareness of the lack of population diversity in GWAS. Interoperability of the Catalog has been enhanced through links to other resources including the Polygenic Score Catalog and the International Mouse Phenotyping Consortium, refinements to GWAS trait annotation, and the development of a standard format for GWAS data.

[Clinical results of tibial pilon fractures treated by open reduction and internal fixation]. / Açik redüksiyon ve internal fiksasyon uygulanan tibia pilon kiriklarinda klinik sonuçlar.

OBJECTIVES: We evaluated the results of pilon fractures treated by open reduction and internal fixation. METHODS: The study included 18 patients (mean age 36 years; range 19 to 56 years) with pilon fractures. According to the Ruedi and Allgower's classification, there were three type I, nine type II, and six type III fractures. Five fractures were open including three of Gustilo-Anderson type II, and two fractures of type III. The results were assessed using the Burwell-Charnley criteria. The mean follow-up was 54 months (range 9 to 86 months). RESULTS: According to the Burwell-Charnley criteria, the results were good in 12 patients (66%), fair in three patients (17%), and poor in three patients (17%). The most common complication was posttraumatic degenerative arthritis, followed by wound infection (22%), Sudeck atrophy (22%), delayed union (17%), and angulation (11%). CONCLUSION: Early anatomical reduction, a stable fixation, early mobilization, and delayed weight-bearing seem to improve long-term results of treatment in pilon fractures caused by high energy trauma.