The analysis of structural variants, in particular of copy-number variations (CNVs), has proven valuable in unraveling the genetic basis of human diseases. Hence, a large number of algorithms have been developed for the detection of CNVs in SNP array signal intensity data. Using the European and African HapMap trio data, we undertook a comparative evaluation of six commonly used CNV detection s...

In 2011, the US Food and drug Administration (FDA) developed a strategic plan for regulatory science that focuses on developing new tools, standards, and approaches to assess the safety, efficacy, quality, and performance of FDA-regulated products. In line with this, the Division of Applied Regulatory Science was created to move new science into the Center for Drug Evaluation and Research (CDER...

Mutations in the first nucleotide of exons (E(+1)) mostly affect pre-mRNA splicing when found in AG-dependent 3' splice sites, whereas AG-independent splice sites are more resistant. The AG-dependency, however, may be difficult to assess just from primary sequence data as it depends on the quality of the polypyrimidine tract. For this reason, in silico prediction tools are commonly used to scor...

The stress responsive transcription factor p53 is a powerful tumor suppressor implicated in over 50 % of all human cancers. The complexity and nonlinear dynamics of p53 network coupled with extensive literature is challenging. Systems biology methodologies offer promising tools to investigate large networks, providing structured in silico representations for integrative analysis. The Boolean p5...

Determining the toxicity of chemicals is necessary to identify their harmful effects on humans, animals, plants, or the environment. It is also one of the main steps in drug design. Animal models have been used for a long time for toxicity testing. However, in vivo animal tests are constrained by time, ethical considerations, and financial burden. Therefore, computational methods for estimating...

The Role of In Silico Tools in Supporting the Application of the Substitution Principle Alessandra Roncaglioni 1, Emilio Benfenati 1, Alberto Mantovani 2, Ferdinando Fiorino 3, Elisa Perissutti 3 and Stefano Lorenzetti 2 Istituto di Ricerche Farmacologiche “Mario Negri” (IRFMN), Department of Environmental Health Sciences, Laboratory of Environmental Toxicology and Chemistry, Milan, Italy; Isti...