Evgeni Tsivtsivadze

Early Respiratory Microbiota Composition Determines Bacterial Succession Patterns and Respiratory Health in Children

RATIONALE Many bacterial pathogens causing respiratory infections in children are common residents of the respiratory tract. Insight into bacterial colonization patterns and microbiota stability at a young age might elucidate healthy or susceptible conditions for development of respiratory disease. OBJECTIVES To study bacterial succession of the respiratory microbiota in the first 2 years of life and its relation to respiratory health characteristics. METHODS Upper respiratory microbiota profiles of 60 healthy children at the ages of 1.5, 6, 12, and 24 months were characterized by 16S-based pyrosequencing. We determined consecutive microbiota profiles by machine-learning algorithms and validated the findings cross-sectionally in an additional cohort of 140 children per age group. MEASUREMENTS AND MAIN RESULTS Overall, we identified eight distinct microbiota profiles in the upper respiratory tract of healthy infants. Profiles could already be identified at 1.5 months of age and were associated with microbiota stability and change over the first 2 years of life. More stable patterns were marked by early presence and high abundance of Moraxella and Corynebacterium/Dolosigranulum and were positively associated with breastfeeding in the first period of life and with lower rates of parental-reported respiratory infections in the consecutive periods. Less stable profiles were marked by high abundance of Haemophilus or Streptococcus. CONCLUSIONS These findings provide novel insights into microbial succession in the respiratory tract in infancy and link early-life profiles to microbiota stability and respiratory health characteristics. New prospective studies should elucidate potential implications of our findings for early diagnosis and prevention of respiratory infections. Clinical trial registered with www.clinicaltrials.gov (NCT00189020).

Lactobacillus-dominated cervicovaginal microbiota associated with reduced HIV/STI prevalence and genital HIV viral load in african women

Cervicovaginal microbiota not dominated by lactobacilli may facilitate transmission of HIV and other sexually transmitted infections (STIs), as well as miscarriages, preterm births and sepsis in pregnant women. However, little is known about the exact nature of the microbiological changes that cause these adverse outcomes. In this study, cervical samples of 174 Rwandan female sex workers were analyzed cross-sectionally using a phylogenetic microarray. Furthermore, HIV-1 RNA concentrations were measured in cervicovaginal lavages of 58 HIV-positive women among them. We identified six microbiome clusters, representing a gradient from low semi-quantitative abundance and diversity dominated by Lactobacillus crispatus (cluster R-I, with R denoting ‘Rwanda’) and L. iners (R-II) to intermediate (R-V) and high abundance and diversity (R-III, R-IV and R-VI) dominated by a mixture of anaerobes, including Gardnerella, Atopobium and Prevotella species. Women in cluster R-I were less likely to have HIV (P=0.03), herpes simplex virus type 2 (HSV-2; P<0.01), and high-risk human papillomavirus (HPV; P<0.01) and had no bacterial STIs (P=0.15). Statistically significant trends in prevalence of viral STIs were found from low prevalence in cluster R-I, to higher prevalence in clusters R-II and R-V, and highest prevalence in clusters R-III/R-IV/R-VI. Furthermore, only 10% of HIV-positive women in clusters R-I/R-II, compared with 40% in cluster R-V, and 42% in clusters R-III/R-IV/R-VI had detectable cervicovaginal HIV-1 RNA (Ptrend=0.03). We conclude that L. crispatus-dominated, and to a lesser extent L. iners-dominated, cervicovaginal microbiota are associated with a lower prevalence of HIV/STIs and a lower likelihood of genital HIV-1 RNA shedding.

An efficient algorithm for learning to rank from preference graphs

In this paper, we introduce a framework for regularized least-squares (RLS) type of ranking cost functions and we propose three such cost functions. Further, we propose a kernel-based preference learning algorithm, which we call RankRLS, for minimizing these functions. It is shown that RankRLS has many computational advantages compared to the ranking algorithms that are based on minimizing other types of costs, such as the hinge cost. In particular, we present efficient algorithms for training, parameter selection, multiple output learning, cross-validation, and large-scale learning. Circumstances under which these computational benefits make RankRLS preferable to RankSVM are considered. We evaluate RankRLS on four different types of ranking tasks using RankSVM and the standard RLS regression as the baselines. RankRLS outperforms the standard RLS regression and its performance is very similar to that of RankSVM, while RankRLS has several computational benefits over RankSVM.

Overview and evaluation of premise selection techniques for large theory mathematics

In this paper, an overview of state-of-the-art techniques for premise selection in large theory mathematics is provided, and new premise selection techniques are introduced. Several evaluation metrics are introduced, compared and their appropriateness is discussed in the context of automated reasoning in large theory mathematics. The methods are evaluated on the MPTP2078 benchmark, a subset of the Mizar library, and a 10% improvement is obtained over the best method so far.

Interindividual variation, correlations, and sex‐related differences in the salivary biochemistry of young healthy adults

A cross-sectional observational study was conducted to evaluate interindividual biochemical variation in unstimulated whole saliva in a population of 268 systemically healthy young students, 18-30 yr of age, with no apparent caries lesions or periodontal disease. Salivary flow rate, protein content, pH, buffering capacity, mucins MUC5B and MUC7, albumin, secretory IgA, cystatin S, lactoferrin, chitinase, amylase, lysozyme, and proteases were measured using ELISAs and enzymatic activity assays. Significant differences were found between male and female subjects. Salivary pH, buffering capacity, protein content, MUC5B, secretory IgA, and chitinase activity were all lower in female subjects compared with male subjects, whereas MUC7 and lysozyme activity were higher in female subjects. There was no significant difference between sexes in salivary flow rate, albumin, cystatin S, amylase, and protease activity. Principal component analysis (PCA) and spectral clustering (SC) were used to assess intervariable relationships within the data set and to identify subgroups. Spectral clustering identified two clusters of participants, which were subsequently described. This study provides a comprehensive overview of the distribution and inter-relations of a set of important salivary biochemical variables in a systemically healthy young adult population, free of apparent caries lesions and periodontal disease. It highlights significant gender differences in salivary biochemistry.

Learning intransitive reciprocal relations with kernel methods

In different fields like decision making, psychology, game theory and biology, it has been observed that paired-comparison data like preference relations defined by humans and animals can be intransitive. Intransitive relations cannot be modeled with existing machine learning methods like ranking models, because these models exhibit strong transitivity properties. More specifically, in a stochastic context, where often the reciprocity property characterizes probabilistic relations such as choice probabilities, it has been formally shown that ranking models always satisfy the well-known strong stochastic transitivity property. Given this limitation of ranking models, we present a new kernel function that together with the regularized least-squares algorithm is capable of inferring intransitive reciprocal relations in problems where transitivity violations cannot be considered as noise. In this approach it is the kernel function that defines the transition from learning transitive to learning intransitive relations, and the Kronecker-product is introduced for representing the latter type of relations. In addition, we empirically demonstrate on two benchmark problems, one in game theory and one in theoretical biology, that our algorithm outperforms methods not capable of learning intransitive reciprocal relations.

Regularized least-squares for parse ranking

We present an adaptation of the Regularized Least-Squares algorithm for the rank learning problem and an application of the method to reranking of the parses produced by the Link Grammar (LG) dependency parser. We study the use of several grammatically motivated features extracted from parses and evaluate the ranker with individual features and the combination of all features on a set of biomedical sentences annotated for syntactic dependencies. Using a parse goodness function based on the F-score, we demonstrate that our method produces a statistically significant increase in rank correlation from 0.18 to 0.42 compared to the built-in ranking heuristics of the LG parser. Further, we analyze the performance of our ranker with respect to the number of sentences and parses per sentence used for training and illustrate that the method is applicable to sparse datasets, showing improved performance with as few as 100 training sentences.

Correlates of the molecular vaginal microbiota composition of African women

BackgroundSociodemographic, behavioral and clinical correlates of the vaginal microbiome (VMB) as characterized by molecular methods have not been adequately studied. VMB dominated by bacteria other than lactobacilli may cause inflammation, which may facilitate HIV acquisition and other adverse reproductive health outcomes.MethodsWe characterized the VMB of women in Kenya, Rwanda, South Africa and Tanzania (KRST) using a 16S rDNA phylogenetic microarray. Cytokines were quantified in cervicovaginal lavages. Potential sociodemographic, behavioral, and clinical correlates were also evaluated.ResultsThree hundred thirteen samples from 230 women were available for analysis. Five VMB clusters were identified: one cluster each dominated by Lactobacillus crispatus (KRST-I) and L. iners (KRST-II), and three clusters not dominated by a single species but containing multiple (facultative) anaerobes (KRST-III/IV/V). Women in clusters KRST-I and II had lower mean concentrations of interleukin (IL)-1α (p < 0.001) and Granulocyte Colony Stimulating Factor (G-CSF) (p = 0.01), but higher concentrations of interferon-γ-induced protein (IP-10) (p < 0.01) than women in clusters KRST-III/IV/V. A lower proportion of women in cluster KRST-I tested positive for bacterial sexually transmitted infections (STIs; ptrend = 0.07) and urinary tract infection (UTI; p = 0.06), and a higher proportion of women in clusters KRST-I and II had vaginal candidiasis (ptrend = 0.09), but these associations did not reach statistical significance. Women who reported unusual vaginal discharge were more likely to belong to clusters KRST-III/IV/V (p = 0.05).ConclusionVaginal dysbiosis in African women was significantly associated with vaginal inflammation; the associations with increased prevalence of STIs and UTI, and decreased prevalence of vaginal candidiasis, should be confirmed in larger studies.

Locality-convolution kernel and its application to dependency parse ranking

We propose a Locality-Convolution (LC) kernel in application to dependency parse ranking. The LC kernel measures parse similarities locally, within a small window constructed around each matching feature. Inside the window it makes use of a position sensitive function to take into account the order of the feature appearance. The similarity between two windows is calculated by computing the product of their common attributes and the kernel value is the sum of the window similarities. We applied the introduced kernel together with Regularized Least-Squares (RLS) algorithm to a dataset containing dependency parses obtained from a manually annotated biomedical corpus of 1100 sentences. Our experiments show that RLS with LC kernel performs better than the baseline method. The results outline the importance of local correlations and the order of feature appearance within the parse. Final validation demonstrates statistically significant increase in parse ranking performance.

Neighborhood co-regularized multi-view spectral clustering of microbiome data

In many unsupervised learning problems data can be available in different representations, often referred to as views. By leveraging information from multiple views we can obtain clustering that is more robust and accurate compared to the one obtained via the individual views. We propose a novel algorithm that is based on neighborhood co-regularization of the clustering hypotheses and that searches for the solution which is consistent across different views. In our empirical evaluation on publicly available datasets, the proposed method outperforms several state-of-the-art clustering algorithms. Furthermore, application of our method to recently collected biomedical data leads to new insights, critical for future research on determinants of the cervicovaginal microbiome and the cervicovaginal microbiome as a risk factor for the transmission of HIV. These insights could have an influence on the interpretation of clinical presentation of women with bacterial vaginosis and treatment decisions.