Nikos Vlassis

VizBin - an application for reference-independent visualization and human-augmented binning of metagenomic data

AbstractBackgroundMetagenomics is limited in its ability to link distinct microbial populations to genetic potential due to a current lack of representative isolate genome sequences. Reference-independent approaches, which exploit for example inherent genomic signatures for the clustering of metagenomic fragments (binning), offer the prospect to resolve and reconstruct population-level genomic complements without the need for prior knowledge.ResultsWe present VizBin, a Java™-based application which offers efficient and intuitive reference-independent visualization of metagenomic datasets from single samples for subsequent human-in-the-loop inspection and binning. The method is based on nonlinear dimension reduction of genomic signatures and exploits the superior pattern recognition capabilities of the human eye-brain system for cluster identification and delineation. We demonstrate the general applicability of VizBin for the analysis of metagenomic sequence data by presenting results from two cellulolytic microbial communities and one human-borne microbial consortium. The superior performance of our application compared to other analogous metagenomic visualization and binning methods is also presented.ConclusionsVizBin can be applied de novo for the visualization and subsequent binning of metagenomic datasets from single samples, and it can be used for the post hoc inspection and refinement of automatically generated bins. Due to its computational efficiency, it can be run on common desktop machines and enables the analysis of complex metagenomic datasets in a matter of minutes. The software implementation is available at https://claczny.github.io/VizBinnunder the BSD License (four-clause) and runs under Microsoft Windows™, Apple Mac OS X™ (10.7 to 10.10), and Linux.

Community-integrated omics links dominance of a microbial generalist to fine-tuned resource usage

Microbial communities are complex and dynamic systems that are primarily structured according to their members’ ecological niches. To investigate how niche breadth (generalist versus specialist lifestyle strategies) relates to ecological success, we develop and apply an integrative workflow for the multi-omic analysis of oleaginous mixed microbial communities from a biological wastewater treatment plant. Time- and space-resolved coupled metabolomic and taxonomic analyses demonstrate that the community-wide lipid accumulation phenotype is associated with the dominance of the generalist bacterium Candidatus Microthrix spp. By integrating population-level genomic reconstructions (reflecting fundamental niches) with transcriptomic and proteomic data (realised niches), we identify finely tuned gene expression governing resource usage by Candidatus Microthrix parvicella over time. Moreover, our results indicate that the fluctuating environmental conditions constrain the accumulation of genetic variation in Candidatus Microthrix parvicella likely due to fitness trade-offs. Based on our observations, niche breadth has to be considered as an important factor for understanding the evolutionary processes governing (microbial) population sizes and structures in situ.

The Role of Metabolomics in the Study of Cancer Biomarkers and in the Development of Diagnostic Tools

This chapter introduces the emerging field of metabolomics and its application in the context of cancer biomarker research. Taking advantage of modern high-throughput technologies, and enhanced computational power, metabolomics has a high potential for cancer biomarker identification and the development of diagnostic tools. This chapter describes current metabolomics technologies used in cancer research, starting with metabolomics sample preparation, elaborating on current analytical methodologies for metabolomics measurement and introducing existing software for data analysis. The last part of this chapter deals with the statistical analysis of very large metabolomics datasets and their relevance for cancer biomarker identification.

Fast correspondences for statistical shape models of brain structures

Statistical shape models based on point distribution models are powerful tools for image segmentation or shape analysis. The most challenging part in the generation of point distribution models is the identification of corresponding landmarks among all training shapes. Since in general the true correspondences are unknown, correspondences are frequently established under the hypothesis that correct correspondences lead to a compact model, which is mostly tackled by continuous optimisation methods. In favour of the prospect of an efficient optimisation, we present a simplified view of the correspondence problem for statistical shape models that is based on point-set registration, the linear assignment problem and mesh fairing. At first, regularised deformable point-set registration is performed and combined with solving the linear assignment problem to obtain correspondences between shapes on a global scale. With that, rough correspondences are established that may not yet be accurate on a local scale. Then, by using a mesh fairing procedure, consensus of the correspondences on a global and local scale among the entire set of shapes is achieved. We demonstrate that for the generation of statistical shape models of deep brain structures, the proposed approach is preferable over existing population-based methods both in terms of a significantly shorter runtime and in terms of an improved quality of the resulting shape model.

Conditions for duality between fluxes and concentrations in biochemical networks

Mathematical and computational modelling of biochemical networks is often done in terms of either the concentrations of molecular species or the fluxes of biochemical reactions. When is mathematical modelling from either perspective equivalent to the other? Mathematical duality translates concepts, theorems or mathematical structures into other concepts, theorems or structures, in a one-to-one manner. We present a novel stoichiometric condition that is necessary and sufficient for duality between unidirectional fluxes and concentrations. Our numerical experiments, with computational models derived from a range of genome-scale biochemical networks, suggest that this flux-concentration duality is a pervasive property of biochemical networks. We also provide a combinatorial characterisation that is sufficient to ensure flux-concentration duality.The condition prescribes that, for every two disjoint sets of molecular species, there is at least one reaction complex that involves species from only one of the two sets. When unidirectional fluxes and molecular species concentrations are dual vectors, this implies that the behaviour of the corresponding biochemical network can be described entirely in terms of either concentrations or unidirectional fluxes.

FastMotif: Spectral Sequence Motif Discovery

MOTIVATIONnSequence discovery tools play a central role in several fields of computational biology. In the framework of Transcription Factor binding studies, most of the existing motif finding algorithms are computationally demanding, and they may not be able to support the increasingly large datasets produced by modern high-throughput sequencing technologies.nnnRESULTSnWe present FastMotif, a new motif discovery algorithm that is built on a recent machine learning technique referred to as Method of Moments. Based on spectral decompositions, our method is robust to model misspecifications and is not prone to locally optimal solutions. We obtain an algorithm that is extremely fast and designed for the analysis of big sequencing data. On HT-Selex data, FastMotif extracts motif profiles that match those computed by various state-of-the-art algorithms, but one order of magnitude faster. We provide a theoretical and numerical analysis of the algorithms robustness and discuss its sensitivity with respect to the free parameters.nnnAVAILABILITY AND IMPLEMENTATIONnThe Matlab code of FastMotif is available from http://lcsb-portal.uni.lu/bioinformatics.nnnCONTACTnvlassis@adobe.comnnnSUPPLEMENTARY INFORMATIONnSupplementary data are available at Bioinformatics online.

GenePEN: analysis of network activity alterations in complex diseases via the pairwise elastic net

Abstract Complex diseases are often characterized by coordinated expression alterations of genes and proteins which are grouped together in a molecular network. Identifying such interconnected and jointly altered gene/protein groups from functional omics data and a given molecular interaction network is a key challenge in bioinformatics. We describe GenePEN, a penalized logistic regression approach for sample classification via convex optimization, using a newly designed Pairwise Elastic Net penalty that favors the selection of discriminative genes/proteins according to their connectedness in a molecular interaction graph. An efficient implementation of the method finds provably optimal solutions on high-dimensional omics data in a few seconds and is freely available at http://lcsb-portal.uni.lu/bioinformatics.

Does Weather Matter?: Causal Analysis of TV Logs

Weather affects our mood and behaviors, and many aspects of our life. When it is sunny, most people become happier; but when it rains, some people get depressed. Despite this evidence and the abundance of data, weather has mostly been overlooked in the machine learning and data science research. This work presents a causal analysis of how weather affects TV watching patterns. We show that some weather attributes, such as pressure and precipitation, cause major changes in TV watching patterns. To the best of our knowledge, this is the first large-scale causal study of the impact of weather on TV watching patterns.

An Interactive Points of Interest Guidance System

In this paper we propose an intelligent user interface for a Point-of-Interest (POI) recommendation system. Our approach solves many challenges, such as learning from passive data, sequential real-time recommendations, Inferring the users propensity to listen to a recommendation, and minimizing recommendation fatigue. We demonstrate our approach on a real world POI data set from Flicker.

Improved Parkinson’s Disease Classification from Diffusion MRI Data by Fisher Vector Descriptors

Due to the complex clinical picture of Parkinson’s disease (PD), the reliable diagnosis of patients is still challenging. A promising approach is the structural characterization of brain areas affected in PD by diffusion magnetic resonance imaging (dMRI). Standard classification methods depend on an accurate non-linear alignment of all images to a common reference template, and are challenged by the resulting huge dimensionality of the extracted feature space. Here, we propose a novel diagnosis pipeline based on the Fisher vector algorithm. This technique allows for a precise encoding into a high-level descriptor of standard diffusion measures like the fractional anisotropy and the mean diffusivity, extracted from the regions of interest (ROIs) typically involved in PD. The obtained low dimensional, fixed-length descriptors are independent of the image alignment and boost the linear separability of the problem in the description space, leading to more efficient and accurate diagnosis. In a test cohort of 50 PD patients and 50 controls, the implemented methodology outperforms previous methods when using a logistic linear regressor for classification of each ROI independently, which are subsequently combined into a single classification decision.