PEDIA: prioritization of exome data by image analysis

Purpose Phenotype information is crucial for the interpretation of genomic variants. So far it has only been accessible for bioinformatics workflows after encoding into clinical terms by expert dysmorphologists. Methods Here, we introduce an approach driven by artificial intelligence that uses portrait photographs for the interpretation of clinical exome data. We measured the value added by computer-assisted image analysis to the diagnostic yield on a cohort consisting of 679 individuals with 105 different monogenic disorders. For each case in the cohort we compiled frontal photos, clinical features, and the disease-causing variants, and simulated multiple exomes of different ethnic backgrounds. Results The additional use of similarity scores from computer-assisted analysis of frontal photos improved the top 1 accuracy rate by more than 20–89% and the top 10 accuracy rate by more than 5–99% for the disease-causing gene. Conclusion Image analysis by deep-learning algorithms can be used to quantify the phenotypic similarity (PP4 criterion of the American College of Medical Genetics and Genomics guidelines) and to advance the performance of bioinformatics pipelines for exome analysis

Insight into the development of a carbonate platform through a multi-disciplinary approach - A case study from the Upper Devonian slope deposits of Mount Freikofel (Carnic Alps, Austria/Italy)

The development and behavior of Million year-scaled depositional sequences recorded within Palaeozoic carbonate platform has remained poorly examined. Therefore, the understanding of palaeoenvironmental changes that occur in geological past is still limited. We herein undertake a multi-disciplinary approach (sedimentology, conodont biostratigraphy, magnetic susceptibility and geochemistry) of a long-term succession in the Carnic Alps which offers new insights into the peculiar evolution of one of the best example of Palaeozoic carbonate platform in Europe. The Freikofel section, located in the central part of the Carnic Alps represents an outstanding succession in a fore-reef setting, extending from the latest Givetian (indet. falsiovalis conodont Zones) to the early Famennian (Lower crepida conodont Zone). Sedimentological analysis allowed to propose a sedimentary model dominated by distal slope and fore-reef slope deposits. The most distal setting is characterized by an autochthonous pelagic sedimentation showing local occurrence of thin-bedded turbiditic deposits. In the fore-reef slope, in a more proximal setting, there is an accumulation of various autochthonous and allochthonous fine- to coarse-grained sediments originated from the interplay of gravity-flow currents derived from the shallow-water and deeper-water area. The temporal evolution of microfacies in the Freikofel section evolves in two main steps corresponding to the Freikofel (Unit 1) and the Pal (Unit 2) Limestones. Distal slope to fore-reef lithologies and associate changes are from base to top of the section: (U1) thick bedded litho- and bioclastic breccia beds with local fining upward sequence and fine-grained mudstone intercalations corresponding, in the fore-reef setting, to the dismantlement of the Eifelian – Frasnian carbonate platform during the early to late Frasnian time (falsiovalis to rhenana superzones) with one of the causes being the Late Givetian major rift pulse; (U2) occurrence of thin-bedded red nodular and cephalopod-bearing limestones with local lithoclastic grainstone intercalations corresponding to a significant deepening of the area and the progressive withdrawal of sedimentary influxes toward the basin, in relation with late Frasnian sea-level rise. Magnetic susceptibility and geochemical analyses were also performed along the Freikofel section and demonstrate the inherent-parallel link existing between variation in magnetic susceptibility values and proxy for terrestrial input. Interpretation of magnetic susceptibility in term of palaeoenvironmental processes reflect that even though distality remains the major parameter influencing magnetic susceptibility values, carbonate production and water agitation also play an important role.Grants IGCP 580 and NAP0017 (DP, ACDS), the FWF P 23775-B17 (TS and EK

High prevalence of BRCA1 stop mutation c.4183C>T in the Tyrolean population: implications for genetic testing

Screening for founder mutations in BRCA1 and BRCA2 has been discussed as a cost-effective testing strategy in certain populations. In this study, comprehensive BRCA1 and BRCA2 testing was performed in a routine diagnostic setting. The prevalence of the BRCA1 stop mutation c.4183C>T, p.(Gln1395Ter), was determined in unselected breast and ovarian cancer patients from different regions in the Tyrol. Cancer registry data were used to evaluate the impact of this mutation on regional cancer incidence. The mutation c.4183C>T was detected in 30.4% of hereditary BRCA1-associated breast and ovarian cancer patients in our cohort. It was also identified in 4.1% of unselected (26% of unselected triple negative) Tyrolean breast cancer patients and 6.8% of unselected ovarian cancer patients from the Lower Inn Valley (LIV) region. Cancer incidences showed a region-specific increase in age-stratified breast and ovarian cancer risk with standardized incidence ratios of 1.23 and 2.13, respectively. We, thus, report a Tyrolean BRCA1 founder mutation that correlates to a local increase in the breast and ovarian cancer risks. On the basis of its high prevalence, we suggest that targeted genetic analysis should be offered to all women with breast or ovarian cancer and ancestry from the LIV region

Austria between “social protection” and “emancipation”: Negotiating global flows, marketization and nostalgia

Focused on Austria, a national context that still ranks amongst the comparatively more affluent and structurally resilient, this chapter examines diverse public discourses formulated in the context of the global and European economic crises since 2008 and their local impact; the economy’s perceived ‘disembedding’ and hypercommodification are shown to lie at the heart of current Austrian concerns, further entrenching a clash between nationalist nostalgia and inclusive multiculturalism, respectively