Mathieu Giraud

The dog and rat olfactory receptor repertoires

BackgroundDogs and rats have a highly developed capability to detect and identify odorant molecules, even at minute concentrations. Previous analyses have shown that the olfactory receptors (ORs) that specifically bind odorant molecules are encoded by the largest gene family sequenced in mammals so far.ResultsWe identified five amino acid patterns characteristic of ORs in the recently sequenced boxer dog and brown Norway rat genomes. Using these patterns, we retrieved 1,094 dog genes and 1,493 rat genes from these shotgun sequences. The retrieved sequences constitute the olfactory receptor repertoires of these two animals. Subsets of 20.3% (for the dog) and 19.5% (for the rat) of these genes were annotated as pseudogenes as they had one or several mutations interrupting their open reading frames. We performed phylogenetic studies and organized these two repertoires into classes, families and subfamilies.ConclusionWe have established a complete or almost complete list of OR genes in the dog and the rat and have compared the sequences of these genes within and between the two species. Our results provide insight into the evolutionary development of these genes and the local amplifications that have led to the specific amplification of many subfamilies. We have also compared the human and rat ORs with the human and mouse OR repertoires.

Not So Many Runs in Strings

Since the work of Kolpakov and Kucherov in [5,6], it is known that ρ(n), the maximal number of runs in a string, is linear in the length nof the string. A lower bound of

Fast multiclonal clusterization of V(D)J recombinations from high-throughput sequencing

3/(1 + \sqrt{5})n \sim 0.927n

The predictive strength of next-generation sequencing MRD detection for relapse compared with current methods in childhood ALL

has been given by Franek and al. [3,4], and upper bounds have been recently provided by Rytter, Puglisi and al., and Crochemore and Ilie (1.6n) [8.7.1]. However, very few properties are known for the ρ(n)/nfunction. We show here by a simple argument that lim n→ ∞ ρ(n)/nexists and that this limit is never reached. Moreover, we further study the asymptotic behavior of ρ p (n), the maximal number of runs with period at most p. We provide a new bound for some microruns : we show that there is no more than 0.971 nruns of period at most 9 in binary strings. Finally, this technique improves the previous best known upper bound, showing that the total number of runs in a binary string of length nis below 1.52n.

Vidjil: A Web Platform for Analysis of High-Throughput Repertoire Sequencing

BackgroundV(D)J recombinations in lymphocytes are essential for immunological diversity. They are also useful markers of pathologies. In leukemia, they are used to quantify the minimal residual disease during patient follow-up. However, the full breadth of lymphocyte diversity is not fully understood.ResultsWe propose new algorithms that process high-throughput sequencing (HTS) data to extract unnamed V(D)J junctions and gather them into clones for quantification. This analysis is based on a seed heuristic and is fast and scalable because in the first phase, no alignment is performed with germline database sequences. The algorithms were applied to TR γ HTS data from a patient with acute lymphoblastic leukemia, and also on data simulating hypermutations. Our methods identified the main clone, as well as additional clones that were not identified with standard protocols.ConclusionsThe proposed algorithms provide new insight into the analysis of high-throughput sequencing data for leukemia, and also to the quantitative assessment of any immunological profile. The methods described here are implemented in a C++ open-source program called Vidjil.

Protein similarity search with subset seeds on a dedicated reconfigurable hardware

To the editor: Minimal residual disease (MRD) monitoring via antigen receptor quantitative polymerase chain reaction (qPCR) is an important predictor of outcome in childhood acute lymphoblastic leukemia (ALL), is rigorously standardized within the EuroMRD consortium and has a greater sensitivity

GPU parallelization of algebraic dynamic programming

Background The B and T lymphocytes are white blood cells playing a key role in the adaptive immunity. A part of their DNA, called the V(D)J recombinations, is specific to each lymphocyte, and enables recognition of specific antigenes. Today, with new sequencing techniques, one can get billions of DNA sequences from these regions. With dedicated Repertoire Sequencing (RepSeq) methods, it is now possible to picture population of lymphocytes, and to monitor more accurately the immune response as well as pathologies such as leukemia. Methods and Results Vidjil is an open-source platform for the interactive analysis of high-throughput sequencing data from lymphocyte recombinations. It contains an algorithm gathering reads into clonotypes according to their V(D)J junctions, a web application made of a sample, experiment and patient database and a visualization for the analysis of clonotypes along the time. Vidjil is implemented in C++, Python and Javascript and licensed under the GPLv3 open-source license. Source code, binaries and a public web server are available at http://www.vidjil.org and at http://bioinfo.lille.inria.fr/vidjil. Using the Vidjil web application consists of four steps: 1. uploading a raw sequence file (typically a FASTQ); 2. running RepSeq analysis software; 3. visualizing the results; 4. annotating the results and saving them for future use. For the end-user, the Vidjil web application needs no specific installation and just requires a connection and a modern web browser. Vidjil is used by labs in hematology or immunology for research and clinical applications.

Bit-parallel multiple pattern matching

With a sharp increase of available DNA and protein sequence data, new precise and fast similarity search methods are needed for large-scale genome and proteome comparisons. Modern seed-based techniques of similarity search (spaced seeds, multiple seeds, subset seeds) provide a better sensitivity/specificity ratio. We present an implementation of such a seed-based technique on a parallel specialized hardware embedding reconfigurable architecture (FPGA), where the FPGA is tightly connected to large capacity Flash memories. This parallel system allows large databases to be fully indexed and rapidly accessed. Compared to traditional approaches presented by the Blastp software, we obtain both a significant speed-up and better results. To the best of our knowledge, this is the first attempt to exploit efficient seed-based algorithms for parallelizing the sequence similarity search.

Cluster of re-configurable nodes for scanning large genomic banks

Algebraic Dynamic Programming (ADP) is a framework to encode a broad range of optimization problems, including common bioinformatics problems like RNA folding or pairwise sequence alignment. The ADP compiler translates such ADP programs into C. As all the ADP problems have similar data dependencies in the dynamic programming tables, a generic parallelization is possible. We updated the compiler to include a parallel backend, launching a large number of independent threads. Depending on the application, we report speedups ranging from 6.1× to 25.8× on a Nvidia GTX 280 through the CUDA libraries.

High-Throughput Immunogenetics for Clinical and Research Applications in Immunohematology: Potential and Challenges

Text matching with errors is a regular task in computational biology. We present an extension of the bit-parallel Wu-Manber algorithm [16] to combine several searches for a pattern into a collection of fixed-length words. We further present an OpenCL parallelization of a redundant index on massively parallel multicore processors, within a framework of searching for similarities with seed-based heuristics. We successfully implemented and ran our algorithms on GPU and multicore CPU. Some speedups obtained are more than 60×.