Alain Giron

A genomic schism in birds revealed by phylogenetic analysis of DNA strings.

The molecular systematics of vertebrates has been based entirely on alignments of primary structures of macromolecules; however, higher order features of DNA sequences not used in traditional studies also contain valuable phylogenetic information. Recent molecular data sets conflict over the phylogenetic placement of flightless birds (ratites - paleognaths), but placement of this clade critically influences interpretation of character change in birds. To help resolve this issue, we applied a new bioinformatics approach to the largest molecular data set currently available. We distilled nearly one megabase (1 million base pairs) of heterogeneous avian genomic DNA from 20 birds and an alligator into genomic signatures, defined as the complete set of frequencies of short sequence motifs (strings), thereby providing a way to directly compare higher order features of nonhomologous DNA sequences. Phylogenetic analysis and principal component analysis of the signatures strongly support the traditional hypothesis of basal ratites and monophyly of the nonratite birds (neognaths) and imply that ratite genomes are linguistically primitive within birds, despite their base compositional similarity to neognath genomes. Our analyses show further that the phylogenetic signal of genomic signatures are strongest among deep splits within vertebrates. Despite clear problems with phylogenetic analysis of genomic signatures, our study raises intriguing issues about the biological and genomic differences that fundamentally differentiate paleognaths and neognaths.

Exploration of Phylogenetic Data using a Global Sequence Analysis Method

BackgroundMolecular 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.ResultsHere 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.ConclusionThe 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.

Differential automatic diagnosis between Alzheimer's disease and frontotemporal dementia based on perfusion SPECT images

OBJECTIVE Alzheimers disease (AD) and frontotemporal dementia (FTD) are among the most frequent neurodegenerative cognitive disorders, but their differential diagnosis is difficult. The aim of this study was to evaluate an automatic method returning the probability that a patient suffers from AD or FTD from the analysis of brain perfusion single photon emission computed tomography images. METHODS AND MATERIALS A set of 116 descriptors corresponding to the average activity in regions of interest was calculated from the images of 82 AD and 91 FTD patients. A set of linear (logistic regression and linear discriminant analysis) and non-linear (support vector machines, k-nearest neighbours, multilayer perceptron and kernel logistic PLS) classification methods was subsequently used to ascertain diagnoses. Validation was carried out by means of the leave-one-out protocol. Diagnoses by the classifier and by four physicians (visual assessment) were compared. Since images were acquired in different hospitals, the impact of the medical centre on the diagnosis of both the classifier and the physicians was investigated. RESULTS Best results were obtained with support vector machine and partial least squares regression coupled with k-nearest neighbours methods (PLS+K-NN), with an overall accuracy of 88%. PLS+K-NN was however considered as the best method since performances obtained with leave-one-out cross-validation were closer to whole-database learning. The performances of the classifier were higher than those of experts (accuracy ranged from 65 to 72%). Physicians found it more difficult to diagnose the images from centres other than their own, and it affected their performances. CONCLUSIONS The performances obtained by the classifier for the differential diagnosis of AD and FTD were found convincing. It could help physicians in daily practice, particularly when visual assessment is inconclusive, or when dealing with multicentre data.

Geometry is a major determinant of flow reversal in proximal aorta

The aim of this study is to quantify aortic backward flow (BF) using phase-contrast cardiovascular magnetic resonance (PC-CMR) and to study its associations with age, indexes of arterial stiffness, and geometry. Although PC-CMR blood flow studies showed a simultaneous presence of BF and forward flow (FF) in the ascending aorta (AA), the relationship between aortic flows and aging as well as arterial stiffness and geometry in healthy volunteers has never been reported. We studied 96 healthy subjects [47 women, 39 ± 15 yr old (19-79 yr)]. Aortic stiffness [arch pulse wave velocity (PWVAO), AA distensibility], geometry (AA diameter and arch length), and parameters related to AA BF and FF (volumes, peaks, and onset times) were estimated from CMR. Applanation tonometry carotid-femoral pulse-wave velocity (PWVCF), carotid augmentation index, and time to return of the reflected pressure wave were assessed. Whereas FF parameters remained unchanged, BF onset time shortened significantly (R(2) = 0.18, P < 0.0001) and BF volume and BF-to-FF peaks ratio increased significantly (R(2) = 0.38 and R(2) = 0.44, respectively, P < 0.0001) with aging. These two latter BF indexes were also related to stiffness indexes (PWVCF, R(2) > 0.30; PWVAO, R(2) > 0.24; and distensibility, R(2) > 0.20, P < 0.001), augmentation index (R(2) > 0.20, P < 0.001), and aortic geometry (AA diameter, R(2) > 0.58; and arch length, R(2) > 0.31, P < 0.001). In multivariate analysis, aortic diameter was the strongest independent correlate of BF beyond age effect. In conclusion, AA BF estimated using PC-CMR increased significantly in terms of magnitude and volume and appeared earlier with aging and was mostly determined by aortic geometry. Thus BF indexes could be relevant markers of subclinical arterial wall alterations.

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

Background 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.

GENSTYLE : exploration and analysis of DNA sequences with genomic signature

GENSTYLE () is a workspace designed for the characterization and classification of nucleotide sequences. Based on the genomic signature paradigm, GENSTYLE focuses on oligonucleotide frequencies in DNA sequences. Users can select sequences of interest in the GENSTYLE companion database, where the whole set of GenBank sequences is grouped per species, or upload their own sequences to work with. Tools for the exploration and analysis of signatures allow (i) identification of the origin of DNA segments (detection of rare species or species for which technical problems prevent fast characterization, such as micro-organisms with slow growth), (ii) analysis of the homogeneity of a genome and isolation of areas with novel functionality (horizontal transfers for example) – and (iii) molecular phylogeny and taxonomy.

Left atrial aging: a cardiac magnetic resonance feature-tracking study.

Importance of left atrial (LA) phasic function evaluation is increasingly recognized for its incremental value in terms of prognosis and risk stratification. LA phasic deformation in the pathway of normal aging has been characterized using echocardiographic speckle tracking. However, no data are available regarding age-related variations using feature-racking (FT) techniques from standard cine magnetic resonance imaging (MRI). We studied 94 healthy adults (41 ± 14 yr, 47 women), who underwent MRI and Doppler echocardiography on the same day for left ventricular (LV) diastolic function evaluation. From cine MRI, longitudinal strain and strain rate, radial motion fraction, and radial relative velocity, respectively, corresponding to the reservoir, conduit, and LA contraction phases, were measured using dedicated FT software. Longitudinal strain and radial motion fraction decreased gradually and significantly with aging for both reservoir (r > 0.31, P < 0.003) and conduit (r > 0.54, P < 0.001) phases, whereas they remained unchanged during the LA contraction phase. Subsequently, the LA contraction-to-reservoir ratio increased significantly with age (r > 0.44, P < 0.001). Longitudinal strain rate and radial relative velocity significantly decreased with age (reservoir: r = 0.39, P < 0.001, conduit: r > 0.54, P < 0.001), and these associations tended to be stronger in women than in men. Finally, associations of LA functional indexes with age were stronger in individuals with lower transmitral early-to-atrial maximal velocity ratio and mitral annulus maximal longitudinal velocity, as well as higher transmitral early maximal-to-mitral annulus maximal longitudinal velocity ratio, highlighting the LV-LA interplay. Age-related changes in LA phasic function indexes were quantified by cine MRI images using a FT technique and were significantly related to age and LV diastolic function.

Analysis of parametric images derived from genomic sequences using neural network based approaches

The exploration of DNA genomic huge sequences (up to several megabases) needs new kind of data representation allowing robust analyses. With the help of the chaos game representation method (CGR), fractal images can be generated, which allow to observe, at a glance, frequencies of words (small sequences of the four bases: G, A, T, C) in DNA sequences. Classification of CGR images and extraction of main features are the issues addressed in this work, using a classical statistical analysis (principal component analysis) and neural networks grounded on curvilinear component analysis algorithm and Kohonen map.

Functional Connectivity’s Degenerate View of Brain Computation

Brain computation relies on effective interactions between ensembles of neurons. In neuroimaging, measures of functional connectivity (FC) aim at statistically quantifying such interactions, often to study normal or pathological cognition. Their capacity to reflect a meaningful variety of patterns as expected from neural computation in relation to cognitive processes remains debated. The relative weights of time-varying local neurophysiological dynamics versus static structural connectivity (SC) in the generation of FC as measured remains unsettled. Empirical evidence features mixed results: from little to significant FC variability and correlation with cognitive functions, within and between participants. We used a unified approach combining multivariate analysis, bootstrap and computational modeling to characterize the potential variety of patterns of FC and SC both qualitatively and quantitatively. Empirical data and simulations from generative models with different dynamical behaviors demonstrated, largely irrespective of FC metrics, that a linear subspace with dimension one or two could explain much of the variability across patterns of FC. On the contrary, the variability across BOLD time-courses could not be reduced to such a small subspace. FC appeared to strongly reflect SC and to be partly governed by a Gaussian process. The main differences between simulated and empirical data related to limitations of DWI-based SC estimation (and SC itself could then be estimated from FC). Above and beyond the limited dynamical range of the BOLD signal itself, measures of FC may offer a degenerate representation of brain interactions, with limited access to the underlying complexity. They feature an invariant common core, reflecting the channel capacity of the network as conditioned by SC, with a limited, though perhaps meaningful residual variability.

Influence of the AGTR1 A1166C Genotype on the Progression of Arterial Stiffness: A 16-Year Longitudinal Study

BACKGROUND We examined the influence of the AGTR1 A1166C genotype on the 16-year evolution of pulse wave velocity (PWV) in a middle-aged population. In a cross-sectional study, we reported that the presence of the AGTR1 1166C allele was associated with higher aortic stiffness compared with the AGTR1 1166AA genotype. METHODS The study was conducted in 259 subjects who underwent 3 health check-ups over 16 years at the Centre IPC-Paris: an initial visit in 1992-1993, an intermediate visit in 1998-1999, and a final visit in 2007-2008. Aortic stiffness was assessed during the 3 visits by measuring carotid-femoral PWV. AGTR1 A1166C polymorphism was assayed by allele-specific oligonucleotide hybridization. RESULTS AGTR1 1166C allele carriers (AC + CC genotypes) had a 35% more pronounced increase in PWV over this 16-year period when compared with the AGTR1 1166AA subjects (3.01 ± 0.32 vs. 1.92 ± 0.23 m/s; P < 0.001). This increase remained significant after adjustment for age, sex, initial PWV values, and changes in blood pressure (+37%; P < 0.05). The genotype-related differences in PWV were only observed at the last visit (i.e., later in life, after the age of 55 years). The effects of this genotype on PWV were not related to the presence of antihypertensive treatment. CONCLUSIONS This is the first long-term longitudinal study indicating that AT1 1166C carriers are at increased risk of pronounced arterial stiffening during aging especially after the age of 55.