Alain Arneodo

Claude Bernard University Lyon 1, Villeurbanne, Rhône-Alpes, France

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Publications (276)796.59 Total impact

  • No preview · Article · Jan 2016 · Applied Physics Letters
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    ABSTRACT: The distribution of refractive indices (RIs) of a living cell contributes in a nonintuitive manner to its optical phase image and quite rarely can be inverted to recover its internal structure. The interpretation of the quantitative phase images of living cells remains a difficult task because (1) we still have very little knowledge on the impact of its internal macromolecular complexes on the local RI and (2) phase changes produced by light propagation through the sample are mixed with diffraction effects by the internal cell bodies. We propose to implement a two-dimensional wavelet-based contour chain detection method to distinguish internal boundaries based on their greatest optical path difference gradients. These contour chains correspond to the highest image phase contrast and follow the local RI inhomogeneities linked to the intracellular structural intricacy. Their statistics and spatial distribution are the morphological indicators suited for comparing cells of different origins and/ or to follow their transformation in pathologic situations. We use this method to compare nonadherent blood cells from primary and laboratory culture origins and to assess the internal transformation of hematopoietic stem cells by the transduction of the BCR-ABL oncogene responsible for the chronic myelogenous leukemia.
    Full-text · Article · Sep 2015 · Journal of Biomedical Optics
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    ABSTRACT: Editor link to download (50 days accessibility for free) Individual plant cells are rather complex mechanical objects. Despite the fact that their wall mechanical strength may be weakened by comparison with their original tissue template, they nevertheless retain some generic properties of the mother tissue, namely the viscoelasticity and the shape of their walls, which are driven by their internal hydrostatic turgor pressure. This viscoelastic behavior, which affects the power-law response of these cells when indented by an atomic force cantilever with a pyramidal tip, is also very sensitive to the culture media. To our knowledge, we develop here an original analyzing method, based on a multiscale decomposition of force-indentation curves, that reveals and quantifies for the first time the nonlinearity of the mechanical response of living single plant cells upon mechanical deformation. Further comparing the nonlinear strain responses of these isolated cells in three different media, we reveal an alteration of their linear bending elastic regime in both hyper- and hypotonic conditions.
    No preview · Article · May 2015 · Biophysical Journal
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    ABSTRACT: Recent analysis of genome-wide epigenetic modification data, mean replication timing (MRT) profiles and chromosome conformation data in mammals have provided increasing evidence that flexibility in replication origin usage is regulated locally by the epigenetic landscape and over larger genomic distances by the 3D chromatin architecture. Here, we review the recent results establishing some link between replication domains and chromatin structural domains in pluripotent and various differentiated cell types in human. We reconcile the originally proposed dichotomic picture of early and late constant timing regions that replicate by multiple rather synchronous origins in separated nuclear compartments of open and closed chromatins, with the U-shaped MRT domains bordered by "master" replication origins specified by a localized (∼200-300kb) zone of open and transcriptionally active chromatin from which a replication wave likely initiates and propagates toward the domain center via a cascade of origin firing. We discuss the relationships between these MRT domains, topologically associated domains and lamina-associated domains. This review sheds a new light on the epigenetically regulated global chromatin reorganization that underlies the loss of pluripotency and the determination of differentiation properties. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
    No preview · Article · Apr 2015 · FEBS letters
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    Hanna Julienne · Benjamin Audit · Alain Arneodo
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    ABSTRACT: Epigenetic regulation of the replication program during mammalian cell differentiation remains poorly understood. We performed an integrative analysis of eleven genome-wide epigenetic profiles at 100 kb resolution of Mean Replication Timing (MRT) data in six human cell lines. Compared to the organization in four chromatin states shared by the five somatic cell lines, embryonic stem cell (ESC) line H1 displays (i) a gene-poor but highly dynamic chromatin state (EC4) associated to histone variant H2AZ rather than a HP1-associated heterochromatin state (C4) and (ii) a mid-S accessible chromatin state with bivalent gene marks instead of a polycomb-repressed heterochromatin state. Plastic MRT regions (≲ 20% of the genome) are predominantly localized at the borders of U-shaped timing domains. Whereas somatic-specific U-domain borders are gene-dense GC-rich regions, 31.6% of H1-specific U-domain borders are early EC4 regions enriched in pluripotency transcription factors NANOG and OCT4 despite being GC poor and gene deserts. Silencing of these ESC-specific "master" replication initiation zones during differentiation corresponds to a loss of H2AZ and an enrichment in H3K9me3 mark characteristic of late replicating C4 heterochromatin. These results shed a new light on the epigenetically regulated global chromatin reorganization that underlies the loss of pluripotency and lineage commitment.
    Full-text · Article · Feb 2015 · PLoS Computational Biology
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    ABSTRACT: As the elementary building block of eukaryotic chromatin, the nucleosome is at the heart of the compromise between the necessity of compacting DNA in the cell nucleus and the required accessibility to regulatory proteins. The recent availability of genome-wide experimental maps of nucleosome positions for many different organisms and cell types has provided an unprecedented opportunity to elucidate to what extent the DNA sequence conditions the primary structure of chromatin and in turn participates in the chromatin-mediated regulation of nuclear functions, such as gene expression and DNA replication. In this study, we use in vivo and in vitro genome-wide nucleosome occupancy data together with the set of nucleosome-free regions (NFRs) predicted by a physical model of nucleosome formation based on sequence-dependent bending properties of the DNA double-helix, to investigate the role of intrinsic nucleosome occupancy in the regulation of the replication spatio-temporal programme in human. We focus our analysis on the so-called replication U/N-domains that were shown to cover about half of the human genome in the germline (skew-N domains) as well as in embryonic stem cells, somatic and HeLa cells (mean replication timing U-domains). The 'master' origins of replication (MaOris) that border these megabase-sized U/N-domains were found to be specified by a few hundred kb wide regions that are hyper-sensitive to DNase I cleavage, hypomethylated, and enriched in epigenetic marks involved in transcription regulation, the hallmarks of localized open chromatin structures. Here we show that replication U/N-domain borders that are conserved in all considered cell lines have an environment highly enriched in nucleosome-excluding-energy barriers, suggesting that these ubiquitous MaOris have been selected during evolution. In contrast, MaOris that are cell-type-specific are mainly regulated epigenetically and are no longer favoured by a local abundance of intrinsic NFRs encoded in the DNA sequence. At the smaller few hundred bp scale of gene promoters, CpG-rich promoters of housekeeping genes found nearby ubiquitous MaOris as well as CpG-poor promoters of tissue-specific genes found nearby cell-type-specific MaOris, both correspond to in vivo NFRs that are not coded as nucleosome-excluding-energy barriers. Whereas the former promoters are likely to correspond to high occupancy transcription factor binding regions, the latter are an illustration that gene regulation in human is typically cell-type-specific.
    Full-text · Article · Jan 2015 · Journal of Physics Condensed Matter
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    ABSTRACT: Background Spike-wave discharges (SWD) found in neuroelectrical recordings are pathognomonic to absence epilepsy. The characteristic spike-wave morphology of the spike-wave complex (SWC) constituents of SWDs can be mathematically described by a subset of possible spectral power and phase values. Morlet wavelet transform (MWT) generates time-frequency representations well-suited to identifying this SWC-associated subset. New methodMWT decompositions of SWDs reveal spectral power concentrated at harmonic frequencies. The phase relationships underlying SWC morphology were identified by calculating the differences between phase values at SWD fundamental frequency from the 2nd, 3rd and 4th harmonics, then using the three phase differences as coordinates to generate a density distribution in a {360°x360°x360°} phase difference space. Strain-specific density distributions were generated from SWDs of mice carrying the Gria4, Gabrg2 or Scn8a mutations to determine whether SWC morphological variants reliably mapped to the same regions of the distribution, and if distribution values could be used to detect SWD.Comparison with existing methodsTo the best of our knowledge, this algorithm is the first to employ spectral phase to quantify SWC morphology, making it possible to computationally distinguish SWC morphological subtypes and detect SWDs.Results/conclusionsProof-of-concept testing of the SWDfinder algorithm shows: (1) a major pattern of variation in SWC morphology maps to one axis of the phase difference distribution, (2) variability between the strain-specific distributions reflects differences in the proportions of SWC subtypes generated during SWD, and (3) regularities in the spectral power and phase profiles of SWCs can be used to detect waveforms possessing SWC-like morphology. Copyright © 2014. Published by Elsevier B.V.
    Full-text · Article · Dec 2014 · Journal of Neuroscience Methods
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    Pierre Kestener · alain arneodo

    Full-text · Dataset · Nov 2014
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    Pierre Kestener · Alain Arneodo

    Full-text · Dataset · Nov 2014
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    ABSTRACT: The three-dimensional (3D) architecture of the mammalian nucleus is now being unraveled thanks to the recent development of chromatin conformation capture (3C) technologies. Here we report the results of a combined multiscale analysis of genome-wide mean replication timing and chromatin conformation data that reveal some intimate relationships between chromatin folding and human DNA replication. We previously described megabase replication N/U-domains as mammalian multiorigin replication units, and showed that their borders are ‘master’ replication initiation zones that likely initiate cascades of origin firing responsible for the stereotypic replication of these domains. Here, we demonstrate that replication N/U-domains correspond to the structural domains of self-interacting chromatin, and that their borders act as insulating regions both in high-throughput 3C (Hi-C) data and high-resolution 3C (4C) experiments. Further analyses of Hi-C data using a graph-theoretical approach reveal that N/U-domain borders are long-distance, interconnected hubs of the chromatin interaction network. Overall, these results and the observation that a well-defined ordering of chromatin states exists from N/U-domain borders to centers suggest that ‘master’ replication initiation zones are at the heart of a high-order, epigenetically controlled 3D organization of the human genome.
    No preview · Article · Nov 2014 · New Journal of Physics
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    Full-text · Dataset · Oct 2014
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    ABSTRACT: The 2D Wavelet-Transform Modulus Maxima (WTMM) method was used to detect microcalcifications (MC) in human breast tissue seen in mammograms and to characterize the fractal geometry of benign and malignant MC clusters. This was done in the context of a preliminary analysis of a small dataset, via a novel way to partition the wavelet-transform space-scale skeleton. For the first time, the estimated 3D fractal structure of a breast lesion was inferred by pairing the information from two separate 2D projected mammographic views of the same breast, i.e. the cranial-caudal (CC) and mediolateral-oblique (MLO) views. As a novelty, we define the "CC-MLO fractal dimension plot", where a "fractal zone" and "Euclidean zones" (non-fractal) are defined. 118 images (59 cases, 25 malignant and 34 benign) obtained from a digital databank of mammograms with known radiologist diagnostics were analyzed to determine which cases would be plotted in the fractal zone and which cases would fall in the Euclidean zones. 92% of malignant breast lesions studied (23 out of 25 cases) were in the fractal zone while 88% of the benign lesions were in the Euclidean zones (30 out of 34 cases). Furthermore, a Bayesian statistical analysis shows that, with 95% credibility, the probability that fractal breast lesions are malignant is between 74% and 98%. Alternatively, with 95% credibility, the probability that Euclidean breast lesions are benign is between 76% and 96%. These results support the notion that the fractal structure of malignant tumors is more likely to be associated with an invasive behavior into the surrounding tissue compared to the less invasive, Euclidean structure of benign tumors. Finally, based on indirect 3D reconstructions from the 2D views, we conjecture that all breast tumors considered in this study, benign and malignant, fractal or Euclidean, restrict their growth to 2-dimensional manifolds within the breast tissue.
    Full-text · Article · Sep 2014 · PLoS ONE
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    ABSTRACT: Besides their large-scale organization in isochores, mammalian genomes display megabase-sized regions, spanning both genes and intergenes, where the strand nucleotide composition asymmetry decreases linearly, possibly due to replication activity. These so-called skew-N domains cover about a third of the human genome and are bordered by two skew upward jumps that were hypothesized to compose a subset of “master” replication origins active in the germline. Skew-N domains were shown to exhibit a particular gene organization. Genes with CpG-rich promoters likely expressed in the germline are over represented near the master replication origins, with large genes being co-oriented with replication fork progression, which suggests some coordination of replication and transcription. In this study, we describe another skew structure that covers ∼13% of the human genome and that is bordered by putative master replication origins similar to the ones flanking skew-N domains. These skew-split-N domains have a shape reminiscent of a N, but split in half, leaving in the center a region of null skew whose length increases with domain size. These central regions (median size ∼860 kb) have a homogeneous composition, i.e. both a null and constant skew and a constant and low GC content. They correspond to heterochromatin gene deserts found in low-GC isochores with an average gene density of 0.81 promoters/Mb as compared to 7.73 promoters/Mb genome wide. The analysis of epigenetic marks and replication timing data confirms that, in these late replicating heterochomatic regions, the initiation of replication is likely to be random. This contrasts with the transcriptionally active euchromatin state found around the bordering well positioned master replication origins. Altogether skew-N domains and skew-split-N domains cover about 50% of the human genome.
    Full-text · Article · Aug 2014 · Computational Biology and Chemistry

  • No preview · Patent · Jul 2014
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    ABSTRACT: We use the wavelet transform modulus maxima (WTMM) method to perform multifractal analysis of the temporal fluctuations of breast skin temperature recorded using infrared (IR) thermography. When investigating thermograms collected from a panel of patients with breast cancer and some female volunteers with healthy breasts, we show that the multifractal complexity of temperature fluctuations observed on intact breast is lost in mammary glands with malignant tumors. These results highlight dynamics IR imaging as a very valuable non-invasive technique for preliminary screening in asymptomatic women to identify those with risk of breast cancer. Besides potential clinical impact, they also shed a new light on physiological changes that may precede anatomical alterations in breast cancer development.
    No preview · Chapter · Jul 2014
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    ABSTRACT: Breast cancer is the most common type of cancer among women and despite recent advances in the medical field, there are still some inherent limitations in the currently used screening techniques. The radiological interpretation of screening X-ray mammograms often leads to over-diagnosis and, as a consequence, to unnecessary traumatic and painful biopsies. Here we propose a computer-aided multifractal analysis of dynamic infrared (IR) imaging as an efficient method for identifying women with risk of breast cancer. Using a wavelet-based multi-scale method to analyze the temporal fluctuations of breast skin temperature collected from a panel of patients with diagnosed breast cancer and some female volunteers with healthy breasts, we show that the multifractal complexity of temperature fluctuations observed in healthy breasts is lost in mammary glands with malignant tumor. Besides potential clinical impact, these results open new perspectives in the investigation of physiological changes that may precede anatomical alterations in breast cancer development.
    Full-text · Article · May 2014 · Frontiers in Physiology
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    ABSTRACT: The duplication of mammalian genomes is under the control of a spatiotemporal program that orchestrates the positioning and the timing of firing of replication origins. The molecular mechanisms coordinating the activation of about [Formula: see text] predicted origins remain poorly understood, partly due to the intrinsic rarity of replication bubbles, making it difficult to purify short nascent strands (SNS). The precise identification of origins based on the high-throughput sequencing of SNS constitutes a new methodological challenge. We propose a new statistical method with a controlled resolution, adapted to the detection of replication origins from SNS data. We detected an average of 80,000 replication origins in different cell lines. To evaluate the consistency between different protocols, we compared SNS detections with bubble trapping detections. This comparison demonstrated a good agreement between genome-wide methods, with 65% of SNS-detected origins validated by bubble trapping, and 44% of bubble trapping origins validated by SNS origins, when compared at the same resolution. We investigated the interplay between the spatial and the temporal programs of replication at fine scales. We show that most of the origins detected in regions replicated in early S phase are shared by all the cell lines investigated whereas cell-type-specific origins tend to be replicated in late S phase. We shed a new light on the key role of CpG islands, by showing that 80% of the origins associated with CGIs are constitutive. Our results further show that at least 76% of CGIs are origins of replication. The analysis of associations with chromatin marks at different timing of cell division revealed new potential epigenetic regulators driving the spatiotemporal activity of replication origins. We highlight the potential role of H4K20me1 and H3K27me3, the coupling of which is correlated with increased efficiency of replication origins, clearly identifying those marks as potential key regulators of replication origins.
    Full-text · Article · May 2014 · PLoS Genetics
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    ABSTRACT: We propose a two-dimensional (2-D) space-scale analysis of fringe patterns collected from a diffraction phase microscope based on the 2-D Morlet wavelet transform. We show that the adaptation of a ridge detection method with anisotropic 2-D Morlet mother wavelets is more efficient for analyzing cellular and high refractive index contrast objects than Fourier filtering methods since it can separate phase from intensity modulations. We compare the performance of this ridge detection method on theoretical and experimental images of polymer microbeads and experimental images collected from living myoblasts.
    Full-text · Article · Mar 2014 · Journal of Biomedical Optics
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    ABSTRACT: Modelling of the appearance and evolution of tumor diseases is one of the major areas of research in modern biomechanics. The understanding of physiological mechanisms of tumors in the context of biomechanics and mechanobiology can provide a basis for developing new diagnostic techniques and oncological diseases treatment. Biomechnical approaches play an increasing part in designing adequate clinical methods for estimating the state and properties of tissues. The nanobiomechanical methods, measuring the mechanical properties of cells, as well as ultrasonic and different thermal techniques (for example, infrared thermography) are rather effective in differentiating between healthy and abnormal tissues. A quantitative analysis of signals and images is an extremely challenging problem, which is still not completely understood. Its solution will allow researchers to evaluate the norm and pathology criteria. The paper is concerned with the multifractal analysis of the breast skin temperature dynamics measured during examination of mammary glands by the infrared thermography method. The evidential differences between temperature signals of healthy and tumorous mammary glands have been revealed. The health status of normal mammary glands is characterized by the existence of multifractal scaling. By contrast, the temperature signals of mammary glands affected with malignant tumor are characterized by homogeneity and monofractality of temperature fluctuation statistics. The objective, differentiating diagnostic criteria for healthy and tumorous mammary gland found during this study essentially increase the predicting capabilities of dynamic infrared thermography as an effective screening tool for detection of mammary gland oncopathology.
    Full-text · Article · Jan 2014
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    E Gerasimova · B Audit · S G Roux · A Khalil · F Argoul · O Naimark · A Arneodo
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    ABSTRACT: The wavelet transform modulus maxima (WTMM) method was used in a multifractal analysis of skin breast temperature time-series recorded using dynamic infrared (IR) thermography. Multifractal scaling was found for healthy breasts as the signature of a continuous change in the shape of the probability density function (pdf) of temperature fluctuations across time scales from similar to 0.3 to 3 s. In contrast, temperature time-series from breasts with malignant tumors showed homogeneous monofractal temperature fluctuations statistics. These results highlight dynamic IR imaging as a very valuable non-invasive technique for preliminary screening in asymptomatic women to identify those with risk of breast cancer. Copyright (C) EPLA, 2013
    Full-text · Article · Dec 2013 · EPL (Europhysics Letters)

Publication Stats

9k Citations
796.59 Total Impact Points


  • 2009-2015
    • Claude Bernard University Lyon 1
      Villeurbanne, Rhône-Alpes, France
  • 2003-2015
    • Ecole normale supérieure de Lyon
      • UMR 5672 - Laboratoire de Physique
      Lyons, Rhône-Alpes, France
  • 2001-2015
    • French National Centre for Scientific Research
      • • Centre of Molecular Genetics
      • • Laboratoire de Biométrie et Biologie Évolutive (LBBE)
      Lutetia Parisorum, Île-de-France, France
  • 2009-2014
    • University of Lyon
      Lyons, Rhône-Alpes, France
  • 2012
    • Université Paris-Sud 11
      • Centre de Génétique Moléculaire (CGM)
      Orsay, Île-de-France, France
  • 1970-2012
    • Centre de Recherche Paul Pascal
      Pessac, Aquitaine, France
  • 2010
    • University of Bordeaux
      Burdeos, Aquitaine, France
  • 2007-2010
    • University of Maine
      • Department Mathematics & Statistics
      Orono, Minnesota, United States
  • 1998-2000
    • Université Bordeaux Montaigne
      Pessac, Aquitaine, France
  • 1991
    • Ecole Normale Supérieure de Paris
      • Laboratoire de Physique Statistique
      Lutetia Parisorum, Île-de-France, France
  • 1987-1991
    • University of Texas at Austin
      • • Center for Nonlinear Dynamics
      • • Department of Physics
      Austin, Texas, United States
  • 1984-1988
    • University of Nice-Sophia Antipolis
      • Laboratoire de Physique de la Matière Condensée (LPMC)
      Nice, Provence-Alpes-Côte d'Azur, France
  • 1985
    • Columbia University
      New York, New York, United States