Genome Alteration Print (GAP): a tool to visualize and mine complex cancer genomic profiles obtained by SNP arrays

GAP, a method for analyzing complex cancer genome profiles from SNP arrays, performs well even with poor quality data and rearranged genome

Tests of achromatic phase shifters performed on the SYNAPSE test bench: a progress report

The achromatic phase shifter (APS) is a component of the Bracewell nulling interferometer studied in preparation for future space missions (viz. Darwin/TPF-I) focusing on spectroscopic study of Earth-like exo-planets. Several possible designs of such an optical subsystem exist. Four approaches were selected for further study. Thales Alenia Space developed a dielectric prism APS. A focus crossing APS prototype was developed by the OCA, Nice, France. A field reversal APS prototype was prepared by the MPIA in Heidelberg, Germany. Centre Spatial de Li\`ege develops a concept based on Fresnel's rhombs. This paper presents a progress report on the current work aiming at evaluating these prototypes on the SYNAPSE test bench at the Institut d'Astrophysique Spatiale in Orsay, France

Analysis of Somatic Alterations in Cancer Genome: From SNP Arrays to Next Generation Sequencing

International audienceIn this chapter we consider basic hypothesis, problem statements and technological and computa- tional solutions for analysis of copy number alterations in tumor genomes. We provide a data mining tech- nique (based on the GAP method described in (Popova et al., 2009)) which allows extraction of absolute copy numbers and allelic contents from the whole genome copy number variation and allelic imbalance profiles obtained by SNP arrays or NGS

Opto-thermo-mechanical numerical simulations of 3 different concepts of infrared achromatic phase shifters

The Darwin/TPF mission aims at detecting directly extra solar planets. It is based on the nulling interferometry, concept proposed by Bracewell in 1978, and developed since 1995 in several European and American laboratories. One of the key optical devices for this technique is the achromatic phase shifter (APS). This optical component is designed to produce a π phase shift over the whole Darwin spectral range (i.e. 6-18 μm), and will be experimentally tested on the NULLTIMATE consortium nulling test bench (Labèque et al). Three different concepts of APS are being simulated: dispersive plates focus crossing and field reversal. In this paper, we show how thermal, mechanical and optical models are merged into a single robust model, allowing a global numerical simulation of the optical component performances. We show how these simulations help us to optimizing the design and present results of the numerical model

Current results of the PERSEE testbench: the cophasing control and the polychromatic null rate

Stabilizing a nulling interferometer at a nanometric level is the key issue to obtain deep null depths. The PERSEE breadboard has been designed to study and optimize the operation of a cophased nulling bench in the most realistic disturbing environment of a space mission. This presentation focuses on the current results of the PERSEE bench. In terms of metrology, we cophased at 0.33 nm rms for the piston and 80 mas rms for the tip/tilt (0.14% of the Airy disk). A Linear Quadratic Gaussian (LQG) control coupled with an unsupervised vibration identification allows us to maintain that level of correction, even with characteristic vibrations of nulling interferometry space missions. These performances, with an accurate design and alignment of the bench, currently lead to a polychromatic unpolarised null depth of 8.9E-6 stabilized at 3E-7 on the [1.65-2.45] \mum spectral band (37% bandwidth).Comment: 17 pages, 10 figures, proceedings of the Optics+Photonics SPIE conference, San Diego, 201

COVID19 Disease Map, a computational knowledge repository of virus-host interaction mechanisms.

Funder: Bundesministerium für Bildung und ForschungFunder: Bundesministerium für Bildung und Forschung (BMBF)We need to effectively combine the knowledge from surging literature with complex datasets to propose mechanistic models of SARS-CoV-2 infection, improving data interpretation and predicting key targets of intervention. Here, we describe a large-scale community effort to build an open access, interoperable and computable repository of COVID-19 molecular mechanisms. The COVID-19 Disease Map (C19DMap) is a graphical, interactive representation of disease-relevant molecular mechanisms linking many knowledge sources. Notably, it is a computational resource for graph-based analyses and disease modelling. To this end, we established a framework of tools, platforms and guidelines necessary for a multifaceted community of biocurators, domain experts, bioinformaticians and computational biologists. The diagrams of the C19DMap, curated from the literature, are integrated with relevant interaction and text mining databases. We demonstrate the application of network analysis and modelling approaches by concrete examples to highlight new testable hypotheses. This framework helps to find signatures of SARS-CoV-2 predisposition, treatment response or prioritisation of drug candidates. Such an approach may help deal with new waves of COVID-19 or similar pandemics in the long-term perspective

Drug-target identification in COVID-19 disease mechanisms using computational systems biology approaches

IntroductionThe COVID-19 Disease Map project is a large-scale community effort uniting 277 scientists from 130 Institutions around the globe. We use high-quality, mechanistic content describing SARS-CoV-2-host interactions and develop interoperable bioinformatic pipelines for novel target identification and drug repurposing. MethodsExtensive community work allowed an impressive step forward in building interfaces between Systems Biology tools and platforms. Our framework can link biomolecules from omics data analysis and computational modelling to dysregulated pathways in a cell-, tissue- or patient-specific manner. Drug repurposing using text mining and AI-assisted analysis identified potential drugs, chemicals and microRNAs that could target the identified key factors.ResultsResults revealed drugs already tested for anti-COVID-19 efficacy, providing a mechanistic context for their mode of action, and drugs already in clinical trials for treating other diseases, never tested against COVID-19. DiscussionThe key advance is that the proposed framework is versatile and expandable, offering a significant upgrade in the arsenal for virus-host interactions and other complex pathologies

ALADDIN: an optimized ground-based precursor for DARWIN

The ALADDIN concept is an integrated Antarctic-based L-band experiment whose purpose is to demonstrate nulling interferometry and to prepare the DARWIN mission. Because of their privileged location, the relatively modest collectors (1 m) and baseline (up to 40 m) are sufficient to achieve a sensitivity (in terms of detectable zodi levels) which is about twice better than that of a nulling instrument on a large interferometer (such as GENIE at the VLTI), and to reach the 20-zodi threshold value identified to carry out the DARWIN precursor science. These numbers are based on a preliminary design study by Alcatel Alenia Space and were obtained using the same simulation software as the one employed for GENIE. The integrated design enables top-level optimization and full access to the light collectors for the duration of the experiment, while reducing the complexity of the nulling breadboard

Conceptual design of the ALADDIN Antarctic nulling interferometer

It is commonly accepted that highly challenging planet finding missions such as Darwin and TPF need precursors on the ground, for both technological demonstration and study of the exozodiacal clouds around potential targets. A first instrument, GENIE, designed to be implemented in the interferometric laboratory of the VLTI, was studied by ESA and scientific/industrial teams. In this paper we present a concept for ALADDIN, an operational nulling instrument to be implemented at Dome C in Antarctica, and discuss the comparison with GENIE from the instrumental point of view. Our preliminary design involves moderate ~1m size telescopes mounted on a 40m long rotating beam allowing baselines up to 30m and feeding a 2-arm nulling beam combiner. When compared to GENIE, the rotating beam design has the advantage of removing the need for both long-stroke delay line and dispersion control equipments. As a side effect, the instrumental arrangement of ALADDIN finds itself more representative of what Darwin will be. Furthermore, critical issues like phase control, photometric balance and instrumental background suppression are expected to be relaxed by the improved atmospheric conditions, lower temperature, and simpler optical trains. Calibration of geometrical stellar leakage will make advantage of the continuously adjustable baseline. As results, a simpler instrument showing improved performance is expected. In conclusion, we see our ALADDIN concept as a valuable alternative to GENIE, with a quite stronger scientific potential and a considerably simplified instrumental design

ALADDIN: a DARWIN Pathfinder Mission on the Antarctic Plateau

International audienc