Mines ParisTech

About: Mines ParisTech is a education organization based out in Paris, France. It is known for research contribution in the topics: Finite element method & Microstructure. The organization has 6564 authors who have published 11676 publications receiving 359898 citations. The organization is also known as: École nationale supérieure des mines de Paris & École des mines de Paris.

Guidelines for splicing analysis in molecular diagnosis derived from a set of 327 combined in silico/in vitro studies on BRCA1 and BRCA2 variants.

Abstract: Assessing the impact of variants of unknown significance (VUS) on splicing is a key issue in molecular diagnosis. This impact can be predicted by in silico tools, but proper evaluation and user guidelines are lacking. To fill this gap, we embarked upon the largest BRCA1 and BRCA2 splice study to date by testing 272 VUSs (327 analyses) within the BRCA splice network of Unicancer. All these VUSs were analyzed by using six tools (splice site prediction by neural network, splice site finder (SSF), MaxEntScan (MES), ESE finder, relative enhancer and silencer classification by unanimous enrichment, and human splicing finder) and the predictions obtained were compared with transcript analysis results. Combining MES and SSF gave 96% sensitivity and 83% specificity for VUSs occurring in the vicinity of consensus splice sites, that is, the surrounding 11 and 14 bases for the 5' and 3' sites, respectively. This study was also an opportunity to define guidelines for transcript analysis along with a tentative classification of splice variants. The guidelines drawn from this large series should be useful for the whole community, particularly in the context of growing sequencing capacities that require robust pipelines for variant interpretation.

Stable models of typed λ-calculi

Abstract: Following Scott, the denotational semantics of programming languages are usually built from the notion of continuous functions. The need for restricted models has been emphasized by Plotkin and Milner, which showed thats continuous function models did not capture all operational properties of ALGOL-like sequential languages. We present new model constructions from a notion of stable function. This requires the introduction of two different orderings between stable functions which give very different cpo structures to the function spaces. We show that Milner's fully abstract model of Plotkin's PCP language only contains stable functions.