An accurate and interpretable model for siRNA efficacy prediction

BACKGROUND: The use of exogenous small interfering RNAs (siRNAs) for gene silencing has quickly become a widespread molecular tool providing a powerful means for gene functional study and new drug target identification. Although considerable progress has been made recently in understanding how the RNAi pathway mediates gene silencing, the design of potent siRNAs remains challenging. RESULTS: We propose a simple linear model combining basic features of siRNA sequences for siRNA efficacy prediction. Trained and tested on a large dataset of siRNA sequences made recently available, it performs as well as more complex state-of-the-art models in terms of potency prediction accuracy, with the advantage of being directly interpretable. The analysis of this linear model allows us to detect and quantify the effect of nucleotide preferences at particular positions, including previously known and new observations. We also detect and quantify a strong propensity of potent siRNAs to contain short asymmetric motifs in their sequence, and show that, surprisingly, these motifs alone contain at least as much relevant information for potency prediction as the nucleotide preferences for particular positions. CONCLUSION: The model proposed for prediction of siRNA potency is as accurate as a state-of-the-art nonlinear model and is easily interpretable in terms of biological features. It is freely available on the web a

Colonisation à court terme par le benthos sur un écosystème artificiel

International audienc

Effects of material composition and face block exposure on the long-term (2014-2018) colonisation of an intertidal RECIF Artificial Reef in the Bay of Seine

International audienceAn experimental artificial reef (AR) with the incorporation of crushed seashells of the queen scallop Aequipecten opercularis was initiated on the intertidal zone of the Bay of Seine in the framework of the INTERREG IVa RECIF project for a everyone year monitoring observations from March 2014 to April 2018. Three block types were operated: eco-friendly material with 20% or 40% of crushed queen scallop shells, and ordinary concrete made from natural aggregates. On the seven blocks analysed at the end of the experiment in 2018, 74 taxa including 32 sessile and 42 motile fauna have been accounted; no difference of taxonomic richness was observed between material and immersion time. The sessile fauna was identified for the six external faces of two blocks aged of four years: horizontal above face (FAB), horizontal below Face (FBE), face oriented offshore (FOF), face oriented inshore (FIN), vertical face oriented west (FEW) and vertical face oriented east (FEA). FBE showed higher taxonomic richness and abundance than the other block faces. FAB exposed to the light showed the lowest abundances. Our observations showed the efficiency of such AR on the intertidal zone accessible at each spring tide, which was easier to survey than in the subtidal zone, where divers must be mobilised to sample blocks

Regional patterns of continental shelf polychaete diversity: examples for the North Sea, English Channel, Irish Sea and Outer Bristol Channel areas

International audiencePolychaetes are a well-represented group in most marine and estuarine environments, both in terms of number of individuals and species; they typically constitute a significant percentage of the total macrofaunal diversity. The aim of our analyses was to characterise the biodiversity and regional distribution patterns of polychaete assemblages from the continental shelf (0-200 m) of the North Sea, English Channel and Irish Sea. Variations in depth and local distribution of sediment types, amongst other environmental factors, are the main factors affecting the pattern of distribution of benthic polychaetes. Here we applied and compared different approaches to draw the diversity pattern of this marine invertebrate group on a regional biogeographical scale, and to identify the main factors structuring these patterns

Neuronal NLRP1 inflammasome activation of Caspase-1 coordinately regulates inflammatory interleukin-1-beta production and axonal degeneration-associated Caspase-6 activation.

Neuronal active Caspase-6 (Casp6) is associated with Alzheimer disease (AD), cognitive impairment, and axonal degeneration. Caspase-1 (Casp1) can activate Casp6 but the expression and functionality of Casp1-activating inflammasomes has not been well-defined in human neurons. Here, we show that primary cultures of human CNS neurons expressed functional Nod-like receptor protein 1 (NLRP1), absent in melanoma 2, and ICE protease activating factor, but not the NLRP3, inflammasome receptor components. NLRP1 neutralizing antibodies in a cell-free system, and NLRP1 siRNAs in neurons hampered stress-induced Casp1 activation. NLRP1 and Casp1 siRNAs also abolished stress-induced Casp6 activation in neurons. The functionality of the NLRP1 inflammasome in serum-deprived neurons was also demonstrated by NLRP1 siRNA-mediated inhibition of speck formation of the apoptosis-associated speck-like protein containing a caspase recruitment domain conjugated to green fluorescent protein. These results indicated a novel stress-induced intraneuronal NLRP1/Casp1/Casp6 pathway. Lipopolysaccharide induced Casp1 and Casp6 activation in wild-type mice brain cortex, but not in that of Nlrp1−/− and Casp1−/− mice. NLRP1 immunopositive neurons were increase