Experience

Positions after PhD

 
 
 
 
 

Research director

LIRMM, CNRS

Jan 2016 – Present Montpellier, France

Responsibilities include:

  • Head of Institute of Computational Biology (2015-2019)
  • Head of French Molecular Bioinformatics network (2010-2016)
  • Head of computer science dpt (2007-2010)
 
 
 
 
 

Reasearcher

LIRMM, CNRS

Jan 2008 – Oct 1999 Montpellier, France
Bioinformatics and algorithmics research.
 
 
 
 
 

Postdoctoral fellow

German Cancer Research Center (Deutsches Krebsforschung Zentrum - DKFZ)

Sep 1996 – Oct 1999 Heidelberg, Germany
Algorithms for transcriptomics.

News

News about software, results, publications, or collaborations

1 min read news
Paper accepted at 31st international COCOON conference

1 min read publication
A collaborative work on the impact of molecular conflicts in the treatment of Multiple Myeloma

1 min read news
Paper accepted at 50th international SOFSEM conference
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Projects

ALL THINGS ARE DIFFICULT BEFORE THEY ARE EASY

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ALPACA

EU funded Int’al Training Network on Computational Pan-Genomics

Superstring

Algorithms for shortest superstring questions

Fast_place

Software for efficient metagenomics and applications to virus metagenomics

GEM

Information fuelled biophysical models for the control of gene expression

FluoRib: impact of chemotherapy on cancer cells’ behavior

Gallery

Illustrations from our projects, bioinformatic services or publications

Recent Publications

Algorithmica
Consider words of length $n$. The set of all periods of a word of length $n$ is a subset of $0,1,2,łdots,n-1$. However, not every subset of $0,1,2,łdots,n-1$ can be a valid set of periods. In a seminal paper in 1981, Guibas and Odlyzko proposed encoding the set of periods of a word into a binary string of length $n$, called an autocorrelation, where a $1$ at position $i$ denotes the period $i$. They considered the question of recognizing a valid period set, and also studied the number $ąppa_n$ of valid period sets for strings of length $n$. They conjectured that $łn p̨pa_n$ asymptotically converges to a constant times $(łn n)^2$. Although improved lower bounds for $łn kp̨a_n/(łn n)^2$ were proved in 2001, the question of a tight upper bound has remained open since Guibas and Odlyzko’s paper. Here, we exhibit an upper bound for this fraction, which implies its convergence and closes this longstanding conjecture. Moreover, we extend our result to find similar bounds for the number of correlations: a generalization of autocorrelations that encodes the overlaps between two strings.
PDF DOI

SOFSEM 2025: Theory and Practice of Computer Science
Overlaps between words are crucial in many areas of computer science, such as code design, stringology, and bioinformatics. A self overlapping word is characterized by its periods and borders. A period of a word u is the starting position of a suffix of u that is also a prefix u, and such a suffix is called a border. Each word of length, say n>0, has a set of periods, but not all combinations of integers are sets of periods. Computing the period set of a word u takes linear time in the length of u. We address the question of computing, the set, denoted $Γ_n$, of all period sets of words of length n. Although period sets have been characterized, there is no formula to compute the cardinality of $Γ_n$ (which is exponential in n), and the known dynamic programming algorithm to enumerate $Γ_n$ suffers from its space complexity. We present an incremental approach to compute $Γ_n$ from $Γ_n-1$, which reduces the space complexity, and then a constructive certification algorithm useful for verification purposes. The incremental approach defines a parental relation between sets in $Γ_n-1$ and $Γ_n$, enabling one to investigate the dynamics of period sets, and their intriguing statistical properties. Moreover, the period set of a word u is key for computing the absence probability of u in random texts. Thus, knowing $Γ_n$ is useful to assess the significance of word statistics, such as the number of missing words in a random text.

Blood Neoplasia
Replication stress exerts an important role in fueling genomic instability characterizing multiple myeloma (MM) evolution and is a leading cause of drug resistance. Normal and malignant plasma cells (PCs) are associated with a high transcriptional stress due to the huge production of immunoglobulins. Transcription-replication conflicts (TRCs), arising from collisions between replication and transcription machineries, can promote tumor progression and represent an Achilles’ heel to cancer cells. We reported a gene signature related to TRCs management (TRC score), overexpressed in malignant vs normal PCs. High TRC score identified patients with MM with a poor prognosis who could benefit from a TRC-enhancing therapy, in independent cohorts of patients with MM treated with high-dose melphalan chemotherapy or anti-CD38 immunotherapy. Here, we investigated the therapeutic interest of increasing TRCs to target specifically malignant PCs using the G-quadruplex (G4) stabilizer pyridostatin (PDS). PDS exerted significant toxicity in MM cell lines and primary MM cells, inducing DNA damage, cell cycle arrest, and apoptosis. Importantly, primary myeloma cells are significantly more sensitive to PDS treatment than normal bone marrow cells. Moreover, PDS improved the efficacy of MM treatments such as melphalan and histone deacetylase (HDAC) or bromodomain (BRD) inhibitors. Thus, our study shows that G4 stabilizers could be used to specifically target MM cells that exhibit concomitant replication stress and a high level of transcription, through the increase of TRCs. These molecules could be used to increase the efficacy of other treatments including melphalan, HDAC inhibitors, and BRD inhibitors.
PDF DOI

Cold Spring Harbor Laboratory
Ancestral sequence reconstruction is an important task in bioinformatics, with applications ranging from protein engineering to the study of genome evolution. When sequences can only undergo substitutions, optimal reconstructions can be efficiently computed using well-known algorithms. However, accounting for indels in ancestral reconstructions is much harder. First, for biologically-relevant problem formulations, no polynomial-time exact algorithms are available. Second, multiple reconstructions are often equally parsimonious or likely, making it crucial to correctly display uncertainty in the results. Here, we consider a parsimony approach where any indel event has the same cost, irrespective of its size or the branch where it occurs. We thoroughly examine the case where only deletions are allowed, while addressing the aforementioned limitations. First, we describe an exact algorithm to obtain all the optimal solutions. The algorithm runs in polynomial time if only one solution is sought. Second, we show that all possible optimal reconstructions for a fixed node can be represented using a graph computable in polynomial time. While previous studies have proposed graph-based representations of ancestral reconstructions, this result is the first to offer a solid mathematical justification for this approach. Finally we discuss the relevance of the deletion-only case for the general case.Competing Interest StatementThe authors have declared no competing interest.
PDF DOI

All routine clinical treatments for colorectal cancer include 5-fluorouracil (5-FU), which cannot counteract recurrence and metastases formation. As the pyrimidine analog 5-FU can impact multiple pathways including both DNA and RNA metabolism, studying its mode of actions could lead to improved therapies. Using a dedicated reporter system for lineage-tracing and deep translatome profiling we demonstrate that 5-FU causes some colorectal cancer cells to tolerate the drug, due to a durable translational reprogramming that sustains cell plasticity. This period of drug tolerance coincides with specific translational activation of genes coding for proteins with major pro-tumoral functions. We unravel a major unexpected translational overexpression of the pro-inflammatory and pro-tumoral IL-8 cytokine, alongside other anti-apoptotic, senescence-associated secretory phenotype and cancer-related senescence phenotype genes. Given the adverse prognostic implications of elevated IL-8 levels across various cancers, our findings suggest IL-8 targeting could counteract 5-FU resistance.
DOI
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Popular Topics

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Contact

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  • (33) 04 67 41 86 64
  • LIRMM - UMR 5506 & University Montpellier (CC 05016) 860 rue de St Priest - 34095 Montpellier cedex 5 FRANCE