MetaboHunter: an automatic approach for identification of metabolites from 1H-NMR spectra of complex mixtures

<p>Abstract</p> <p>Background</p> <p>One-dimensional ¹H-NMR spectroscopy is widely used for high-throughput characterization of metabolites in complex biological mixtures. However, the accurate identification of individual compounds is still a challenging task, particularly in spectral regions with higher peak densities. The need for automatic tools to facilitate and further improve the accuracy of such tasks, while using increasingly larger reference spectral libraries becomes a priority of current metabolomics research.</p> <p>Results</p> <p>We introduce a web server application, called MetaboHunter, which can be used for automatic assignment of ¹H-NMR spectra of metabolites. MetaboHunter provides methods for automatic metabolite identification based on spectra or peak lists with three different search methods and with possibility for peak drift in a user defined spectral range. The assignment is performed using as reference libraries manually curated data from two major publicly available databases of NMR metabolite standard measurements (HMDB and MMCD). Tests using a variety of synthetic and experimental spectra of single and multi metabolite mixtures show that MetaboHunter is able to identify, in average, more than 80% of detectable metabolites from spectra of synthetic mixtures and more than 50% from spectra corresponding to experimental mixtures. This work also suggests that better scoring functions improve by more than 30% the performance of MetaboHunter's metabolite identification methods.</p> <p>Conclusions</p> <p>MetaboHunter is a freely accessible, easy to use and user friendly ¹H-NMR-based web server application that provides efficient data input and pre-processing, flexible parameter settings, fast and automatic metabolite fingerprinting and results visualization via intuitive plotting and compound peak hit maps. Compared to other published and freely accessible metabolomics tools, MetaboHunter implements three efficient methods to search for metabolites in manually curated data from two reference libraries.</p> <p>Availability</p> <p><url>http://www.nrcbioinformatics.ca/metabohunter/</url></p

Fuzzy J-Means and VNS Methods for Clustering Genes from Microarray Data *

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A surrogate signal model for automated 1D 1H NMR compound quantification

Bioreactors are useful tools for bioprocessing and production of biologics, gene therapies and vaccines. Streaming data-driven process control systems can be valuable in lowering the cost of production or discovering novel reaction pathways. Nuclear Magnetic resonance (NMR) is an inexpensive spectroscopy technique that has characteristics that make it appropriate for on-line, high-throughput measurement of metabolic changes in a bioreactor vessel. Future quantitative NMR (qNMR) advancements for processing this type of streaming data could grant a unique possibility for in-situ bioprocessing applications. One significant challenge for 1D 1H qNMR is that the spectrum of a compound can deviate from its spectrum in a reference setting, especially across the various spectrometer frequency and concentration profile of metabolite mixture in the biofluid sample. A robust predictive or constraint model on the generative mechanism of the measured NMR signal can help guide future qNMR developments. We present an approximated 1D 1H NMR signal model that shows promise in fitting chemical shifts and other interpretable parameters for small mixtures of compounds. Our model use reference chemistry parameters of compounds to derive patterns between its nuclei via spin Hamiltonian simulations and hierarchical convex clustering on a spin angular momentum feature between the nuclei, which are quantum subsystems. These patterns are used to construct a surrogate model of the compound mixture with a lower degrees-of-freedom. Our approach does not require any phase or baseline correction techniques to pre-process the data, making it a generative model that fully accounts for the relative phase information, which is usually attenuated in a heuristic manner and ignored in conventional NMR data processing. We demonstrate the potential of this new methodology by fitting against real-world NMR reference compound experiments

Dementia with Lewy bodies post-mortem brains reveal differentially methylated CpG sites with biomarker potential

Dementia with Lewy bodies (DLB) is a common form of dementia with known genetic and environmental interactions. However, the underlying epigenetic mechanisms which reflect these gene-environment interactions are poorly studied. Herein, we measure genome-wide DNA methylation profiles of post-mortem brain tissue (Broadmann area 7) from 15 pathologically confirmed DLB brains and compare them with 16 cognitively normal controls using Illumina MethylationEPIC arrays. We identify 17 significantly differentially methylated CpGs (DMCs) and 17 differentially methylated regions (DMRs) between the groups. The DMCs are mainly located at the CpG islands, promoter and first exon regions. Genes associated with the DMCs are linked to “Parkinson’s disease” and “metabolic pathway”, as well as the diseases of “severe intellectual disability” and “mood disorders”. Overall, our study highlights previously unreported DMCs offering insights into DLB pathogenesis with the possibility that some of these could be used as biomarkers of DLB in the future