Exploration of phylogenetic data using a global sequence analysis method

BACKGROUND: Molecular phylogenetic methods are based on alignments of nucleic or peptidic sequences. The tremendous increase in molecular data permits phylogenetic analyses of very long sequences and of many species, but also requires methods to help manage large datasets. RESULTS: Here we explore the phylogenetic signal present in molecular data by genomic signatures, defined as the set of frequencies of short oligonucleotides present in DNA sequences. Although violating many of the standard assumptions of traditional phylogenetic analyses – in particular explicit statements of homology inherent in character matrices – the use of the signature does permit the analysis of very long sequences, even those that are unalignable, and is therefore most useful in cases where alignment is questionable. We compare the results obtained by traditional phylogenetic methods to those inferred by the signature method for two genes: RAG1, which is easily alignable, and 18S RNA, where alignments are often ambiguous for some regions. We also apply this method to a multigene data set of 33 genes for 9 bacteria and one archea species as well as to the whole genome of a set of 16 γ-proteobacteria. In addition to delivering phylogenetic results comparable to traditional methods, the comparison of signatures for the sequences involved in the bacterial example identified putative candidates for horizontal gene transfers. CONCLUSION: The signature method is therefore a fast tool for exploring phylogenetic data, providing not only a pretreatment for discovering new sequence relationships, but also for identifying cases of sequence evolution that could confound traditional phylogenetic analysis

Detection of melanoma from dermoscopic images of naevi acquired under uncontrolled conditions.

International audienceBACKGROUND AND OBJECTIVE: Several systems for the diagnosis of melanoma from images of naevi obtained under controlled conditions have demonstrated comparable efficiency with dermatologists. However, their robustness to analyze daily routine images was sometimes questionable. The purpose of this work is to investigate to what extent the automatic melanoma diagnosis may be achieved from the analysis of uncontrolled images of pigmented skin lesions. MATERIALS AND METHODS: Images were acquired during regular practice by two dermatologists using Reflex 24 x 36 cameras combined with Heine Delta 10 dermascopes. The images were then digitalized using a scanner. In addition, five senior dermatologists were asked to give the diagnosis and therapeutic decision (exeresis) for 227 images of naevi, together with an opinion about the existence of malignancy-predictive features. Meanwhile, a learning by sample classifier for the diagnosis of melanoma was constructed, which combines image-processing with machine-learning techniques. After an automatic segmentation, geometric and colorimetric parameters were extracted from images and selected according to their efficiency in predicting malignancy features. A diagnosis was subsequently provided based on selected parameters. An extensive comparison of dermatologists' and computer results was subsequently performed. RESULTS AND CONCLUSION: The KL-PLS-based classifier shows comparable performances with respect to dermatologists (sensitivity: 95% and specificity: 60%). The algorithm provides an original insight into the clinical knowledge of pigmented skin lesions

Low-dose hyper-radiosensitivity of progressive and regressive cells isolated from a rat colon tumour: impact of DNA repair.

International audiencePURPOSE: To ask whether highly metastatic sublines show more marked low-dose hyper-radiosensitivity (HRS) response than poorly metastatic ones. MATERIALS AND METHODS: The progressive (PRO) subline showing tumourigenicity and metastatic potential and the regressive (REG) subline showing neither tumourigenicity nor metastatic potential were both isolated from a parental rat colon tumour. Clonogenic survival, micronuclei and apoptosis, cell cycle distribution, DNA single- (SSB) and double-strand breaks (DSB) induction and repair were examined. RESULTS: HRS phenomenon was demonstrated in PRO subline. Before irradiation, PRO cells show more spontaneous damage than REG cells. After 0.1 Gy, PRO cells displayed: (i) More DNA SSB 15 min post-irradiation, (ii) more unrepaired DNA DSB processed by the non-homologous end-joining (NHEJ) and by the RAD51-dependent recombination pathways, (iii) more micronuclei, than REG cells while neither apoptosis nor p53 phosphorylation nor cell cycle arrest was observed in both sublines. CONCLUSIONS: HRS response of PRO subline may be induced by impairments in NHEJ repair that targets G(1) cells and RAD51-dependent repair that targets S-G(2)/M cells. The cellular consequences of such impairments are a failure to arrest in cell cycle, the propagation of damage through cell cycle, mitotic death but not p53-dependent apoptosis. Tumourigenic cells with high metastatic potential may preferentially show HRS response

Automatic classification of skin lesions using geometrical measurements of adaptive neighborhoods and local binary patterns

ISBN:978-1-4799-8339-1International audienceThis paper introduces a method for characterizing and classifying skin lesions in dermoscopic color images with the goal of detecting which ones are melanoma (cancerous lesions). The images are described by means of the Local Binary Patterns (LBPs) computed on geometrical feature maps of each color component of the image. These maps are extracted from geometrical measurements of the General Adaptive Neighborhoods (GAN) of the pixels. The GAN of a pixel is a region surrounding it and fitting its local image spatial structure. The performance of the proposed texture descriptor has been evaluated by means of an Artificial Neural Network, and it has been compared with the classical LBPs. Experimental results using ROC curves show that the GAN-based method outperforms the classical one and the dermatologists' predictions

Automatic classification of skin lesions using color mathematical morphology-based texture descriptors

SPIE : Society of Photo-Optical Instrumentation EngineersInternational audienceIn this paper an automatic classification method of skin lesions from dermoscopic images is proposed. This method is based on color texture analysis based both on color mathematical morphology and Kohonen Self-Organizing Maps (SOM), and it does not need any previous segmentation process. More concretely, mathematical morphology is used to compute a local descriptor for each pixel of the image, while the SOM is used to cluster them and, thus, create the texture descriptor of the global image. Two approaches are proposed, depending on whether the pixel descriptor is computed using classical (i.e. spatially invariant) or adaptive (i.e. spatially variant) mathematical morphology by means of the Color Adaptive Neighborhoods (CANs) framework. Both approaches obtained similar areas under the ROC curve (AUC): 0.854 and 0.859 outperforming the AUC built upon dermatologists' predictions (0.792)

Texture descriptors based on adaptive neighborhoods for classification of pigmented skin lesions

art. 061104Se proponen diferentes descriptores de textura para la clasificación automática de lesiones cutáneas a partir de imágenes dermoscópicas. Se basan en el análisis de textura de color obtenido de (1) morfología matemática del color (MM) y mapas autoorganizativos de Kohonen (SOM) o (2) patrones binarios locales (LBP), calculados con el uso de barrios adaptativos locales de la imagen. Ninguno de estos dos enfoques necesita un proceso de segmentación anterior. En el primer descriptor propuesto, los barrios adaptativos se utilizan como elementos de estructuración para llevar a cabo operaciones MM adaptables que se combinan aún más mediante el uso de KOhonen SOM; esto se ha comparado con una versión no adaptativa. En la segunda, las vecindades adaptables permiten definir mapas de entidades geométricas, a partir de los cuales se calculan histogramas LBP. Esto también se ha comparado con un enfoque clásico de LBP. Un análisis de las características operativas del receptor de los resultados experimentales muestra que el enfoque adaptativo de LBP basado en la vecindad produce los mejores resultados. Supera a las versiones no adaptativas de los descriptores propuestos y las predicciones visuales de los dermatólogos.S

Sensitivity of human melanoma cells to adherent leukocytes depends on the ratio between them, the activation status of adherent leukocytes and the metastatic potential of tumor cells.

International audienceThis study examined the interaction of the poorly metastatic human melanoma cell line M4Be and the highly metastatic clone 4 derived from M4Be, with respect to fresh adherent leukocytes (AL) isolated from 17 different healthy blood donors. These AL contained 80% (73%-93%) monocytes, 15% (6%-20%) B lymphocytes and 5% (1%-8%) T lymphocytes. The survival of these tumor cells against the stress exerted by these AL was estimated with a clonogenic assay where isolated tumor cells were co-cultured for 14 days in contact with AL and lipopolysaccharide (LPS). For a given blood donor, AL either stimulates or inhibits the colony formation of the tumor cells (T) depending on the AL/T ratio, the AL activation status and the metastatic potential of tumor cells. At low AL/T ratios ( 10/1), whatever the characteristics of the blood donor, clone 4 is significantly more sensitive than M4Be to AL activated with medium containing low (8 ng/ml) or high (1,000 ng/ml) levels of LPS; this killing effect is suggested to be due to TNF-alpha, both soluble and membrane-bound, but not to be due to release of H2O2. These data suggest that the regulatory role of AL, which remove the majority of human melanoma cells and stimulate the colony formation of a small fraction of them, is partly due to TNF-alpha

Quantification de la progression virale dans les rétinopathies à CMV par des techniques d'analyse d'images fondées sur des méthodes d'apprentissage par l'exemple

La rétinite à cytomégalovirus (CMV) est l'infection oculaire opportuniste la plus fréquente et la première cause de cécité chez les malades du SIDA. Elle est caractérisée par une plage de nécrose rétinienne. Sans traitement, la progression de la rétinite se traduit par une extension irréversible de l'infection sous la forme d'un front de nécrose active. Un suivi ophtalmologique régulier de la rétinite à CMV doit donc être instauré. L'enjeu de cette thèse est de mettre au point une méthode permettant, par la comparaison d'angiographies numérisées, de quantifier de façon précise l'avancée du front de nécrose. Il serait ainsi possible d'apprécier et de comparer l'efficacité des traitements et de dépister précocement les récidives éventuelles. Notre approche repose sur deux étapes : la Segmentation des images et la Comparaison des zones segmentées. Compte tenu de la grande variabilité (de formes, de texture, de contraste) des régions d'une angiographie à l'autre et 'un individu à l'autre, les méthodes classiques de segmentation peuvent être difficilement utilisées dans le cadre d'applications devant fonctionner en routine clinique. Nous proposons d'éviter la phase critique de segmentation, en construisant un ensemble d'images dérivées de chaque angiographie où seront identifiées les régions de rétine saine et de rétine pathologique, à l'aide d'une méthode neuromimétique de type vision direct, fonctionnant par apprentissage en s'appuyant sur l'expérience des cliniciens. La seconde étape consiste, après une phase de recalage, à apprécier l'évolution de la zone infectée afin d'évaluer la progression virale. Une telle étude nécessite au préalable de juger de la pertinence statistique des mesures rendant comptes de l'avancée du front de rétinite. Ainsi au cours de cette étape, on s'est intéressé à la caractérisation de la précision locale des fronts de nécrose afin de déterminer si la différence observée entre deux frontières est significative ou non. Une étude quantitative sur une centaine d'images d'angiographie de la rétine a permis de valider notre système d'analyse, en comparant nos résultats avec ceux des praticiens. L'approche proposée permet de quantifier de manière objective et reproductible la progression de la rétinite à CMV au cours du temps.PARIS5-BU Méd.Cochin (751142101) / SudocSudocFranceF

Style du génome exploré par analyse textuelle de l'ADN

PARIS-BIUSJ-Thèses (751052125) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF