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Biomedical subjects

Aidong Zhang

Publications and source records attributed to Aidong Zhang.

15 recordsLinked to original sources

ConceptDrift: leveraging spatial, temporal and semantic evolution of biomedical concepts for hypothesis generation.

MOTIVATION: Hypothesis generation is a fundamental problem in biomedical text mining that aims to generate ideas that are new, interesting, and plausible by discovering unexplored links between biomedical concepts. Despite significant advances made by existing approaches, they do not fully leverage the evolutionary properties of biomedical concepts. This is limiting because scientific knowledge continually evolves over time, with new facts being added and old ones becoming obsolete. Thus, it is crucial to capture the evolutionary properties of biomedical concepts from multiple perspectives (e.g. spatial, temporal, and semantic) to generate hypotheses that reflect the up-to-date information landscape of the biomedical domain. RESULTS: We introduce a novel framework, ConceptDrift, that models the hypothesis generation task as a sequence of temporal graphlets and simultaneously encodes spatial, temporal, and semantic change. Unlike existing approaches that treat these dimensions independently, ConceptDrift is the first to provide a holistic understanding of concept evolution by integrating them into a unified framework. Grounded in the theories of the Distributional Hypothesis and Conceptual Change, our method adapts these principles to the unique challenges of large-scale biomedical literature. We conduct extensive experiments across multiple datasets and demonstrate that ConceptDrift consistently outperforms state-of-the-art baselines in generating accurate and meaningful hypotheses. Our framework shows immediate practical benefits for web-based literature mining tools in life sciences and biomedicine, offering more robust and predictive feature representations. AVAILABILITY AND IMPLEMENTATION: https://github.com/amir-hassan25/ConceptDrift (DOI: 10.6084/m9.figshare.29975476).

Semantics↗

An amperometric acetylthiocholine sensor based on immobilization of acetylcholinesterase on a multiwall carbon nanotube-cross-linked chitosan composite.

A simple method has been devised for immobilization of acetylcholinesterase (AChE)--covalent bonding to a multiwall carbon nanotube (MWNT)--cross-linked chitosan composite (CMC)-and a sensitive amperometric sensor for rapid detection of acetylthiocholine (ATCl) has been based on this. Fourier-transform infrared spectroscopy proved that the native structure of the immobilized enzyme was preserved on this chemically clean and homogeneous composite film, because of the excellent biocompatibility and non-toxicity of chitosan. Glutaraldehyde was used as cross-linker to covalently bond the AChE, and efficiently prevented leakage of the enzyme from the film. Because of the inherent conductive properties of the MWNT, the immobilized AChE had greater affinity for ATCl and excellent catalytic effect in the hydrolysis of ATCl, with a K(app)(m) value of 132 micromol L(-1), forming thiocholine, which was then oxidized to produce a detectable and rapid response. Under optimum conditions the amperometric current increased linearly with the increasing concentration of ATCl in the range 2.0-400 micromol L(-1), with a detection limit of 0.10 micromol L(-1). Fabrication reproducibility of the sensor was good and the stability was acceptable. The sensor is a promising new tool for characterization of enzyme inhibitors and for pesticide analysis. Abstract.

Acetylcholinesterase↗

A novel functional module detection algorithm for protein-protein interaction networks.

BACKGROUND: The sparse connectivity of protein-protein interaction data sets makes identification of functional modules challenging. The purpose of this study is to critically evaluate a novel clustering technique for clustering and detecting functional modules in protein-protein interaction networks, termed STM. RESULTS: STM selects representative proteins for each cluster and iteratively refines clusters based on a combination of the signal transduced and graph topology. STM is found to be effective at detecting clusters with a diverse range of interaction structures that are significant on measures of biological relevance. The STM approach is compared to six competing approaches including the maximum clique, quasi-clique, minimum cut, betweeness cut and Markov Clustering (MCL) algorithms. The clusters obtained by each technique are compared for enrichment of biological function. STM generates larger clusters and the clusters identified have p-values that are approximately 125-fold better than the other methods on biological function. An important strength of STM is that the percentage of proteins that are discarded to create clusters is much lower than the other approaches. CONCLUSION: STM outperforms competing approaches and is capable of effectively detecting both densely and sparsely connected, biologically relevant functional modules with fewer discards.

Journal Article↗

Information-theoretic identification of predictive SNPs and supervised visualization of genome-wide association studies.

The size, dimensionality and the limited range of the data values makes visualization of single nucleotide polymorphism (SNP) datasets challenging. The purpose of this study is to evaluate the usefulness of 3D VizStruct, a novel multi-dimensional data visualization technique for SNP datasets capable of identifying informative SNPs in genome-wide association studies. VizStruct is an interactive visualization technique that reduces multi-dimensional data to three dimensions using a combination of the discrete Fourier transform and the Kullback-Leibler divergence. The performance of 3D VizStruct was challenged with several diverse, biologically relevant published datasets including the human lipoprotein lipase (LPL) gene locus, the human Y-chromosome in several populations and a multi-locus genotype dataset of coral samples from four populations. In every case, the SNPs and or polymorphic markers identified by the 3D VizStruct mapping were predictive of the underlying biology.

Animals↗

A novel detection strategy for odorant molecules based on controlled bioengineering of rat olfactory receptor I7.

In this study, we report a dose-dependent detection of odorant molecules in solution by rat olfactory receptor I7 (OR I7) in its membrane fraction. The OR I7 is immobilized on a gold electrode by multilayer bioengineering based on a mixed self-assembled monolayer and biotin/avidin system, which allows for a well-controlled immobilization of the bioreceptor within its lipid environment. The odorant detection is electronically performed in a quantitative manner by electrochemical impedance spectroscopy (EIS) measurements on samples and controls.

Animals↗

VizStruct for visualization of genome-wide SNP analyses.

MOTIVATION: The size, dimensionality and the limited range of the data values make visualization of single nucleotide polymorphism (SNP) datasets challenging. The purpose of this study is to evaluate the usefulness of 3D VizStruct, a novel multi-dimensional data visualization technique for analyzing patterns in SNP datasets. RESULTS: VizStruct is an interactive visualization technique that reduces multi-dimensional data to two dimensions using the complex-valued harmonics of the discrete Fourier transform (DFT). In the 3D VizStruct extension, the multi-dimensional SNP data vectors are reduced to three dimensions using a combination of the DFT and the Kullback-Leibler divergence. The performance of 3D VizStruct was challenged with several biologically relevant published datasets that included human Chromosome 21, the human lipoprotein lipase (LPL) gene locus and the multi-locus genotypes of coral populations. In every case, the 3D VizStruct mapping provided an intuitive visual description of the key characteristics of the underlying multi-dimensional genotype.

Animals↗

Immobilization of rhodopsin on a self-assembled multilayer and its specific detection by electrochemical impedance spectroscopy.

Rhodopsin, the G protein-coupled receptor (GPCR) which mediates the sense of vision, was prepared from calf eyes and used as receptor enriched membrane fraction. In this study it was immobilized onto gold electrode by two different techniques: Langmuir-Blodgett (LB) and a strategy based on a self-assembled multilayer. We demonstrated that Langmuir and LB films of rhodopsin are not stable. Thus, in this study a new protein multilayer was prepared on gold electrode by building up layer-by-layer a self-assembled multilayer. It is composed of a mixed self-assembled monolayer formed by MHDA and biotinyl-PE, followed by a biotin-avidin system which allows binding of biotinylated antibody specific to rhodopsin. The immobilization of rhodopsin in membrane fraction, by the specific antibody bound previously on self-assembled multilayer, was monitored with electrochemical impedance spectroscopy (EIS). In addition, the specificity and sensitivity of this self-assembled multilayer system to the presence of rhodopsin were investigated. No effect was observed when the system was in contact with olfactory receptor I7 in membrane fraction used for control measurements. All these results demonstrate that rhodopsin can be immobilized efficiently, specifically, quantitatively and stably on gold electrode through the self-assembled multilayer.

Adsorption↗

Study of Langmuir and Langmuir-Blodgett films of odorant-binding protein/amphiphile for odorant biosensors.

To make ultrathin films for the fabrication of artificial olfactory systems, odorant biosensors, we have investigated mixed Langmuir and Langmuir-Blodgett films of odorant-binding protein/amphiphile. Under optimized experimental conditions (phosphate buffer solution, pH 7.5, OBP-1F concentration of 4 mg L(-1), target pressure 35 mN m(-1)), the mixed monolayer at the air/water interface is very stable and has been efficiently transferred onto gold supports, which were previously functionalized by self-assembled monolayers (SAMs) with 1-octadecanethiol (ODT). Atomic force microscopy and electrochemical impedance spectroscopy were used to characterize mixed Langmuir-Blodgett (LB) films before and after contact with a specific odorant molecule, isoamyl acetate. AFM phase images show a higher contrast after contact with the odorant molecule due to the new structure of the OBP-1F/ODA LB film. Non-Faradaic electrochemical spectroscopy (EIS) is used to quantify the effect of the odorant based on the electrical properties of the OBP-1F/ODA LB film, as its resistance strongly decreases from 1.18 MOmega (before contact) to 25 kOmega (after contact).

Adsorption↗

A topological measurement for weighted protein interaction network.

High-throughput methods for detecting protein-protein interactions (PPI) have given researchers an initial global picture of protein interactions on a genomic scale. The usefulness of this understanding is, however, typically compromised by noisy data. The effective way of integrating and using these non-congruent data sets has received little attention to date. This paper proposes a model to integrate different data sets. We construct this model using our prior knowledge of data set reliability. Based on this model, we propose a topological measurement to select reliable interactions and to quantify the similarity between two proteins' interaction profiles. Our measurement exploits the small-world network topological properties of protein interaction network. Meanwhile, we discovered some additional properties of the network. We show that our measurement can be used to find reliable interactions with improved performance and to find protein pairs with higher function homogeneity.

Algorithms↗

Study of mixed Langmuir-Blodgett films of immunoglobulin G/amphiphile and their application for immunosensor engineering.

Langmuir-Blodgett (LB) technique appears to be quite suitable for generating biospecific surfaces and it has potential application for fabricating biosensors. In this work, mixed Langmuir-Blodgett films of immunoglobulin G/amphiphile have been transferred onto hydrophobic silver surface previously modified by 1-octadecanethiol (ODT) SAMs. In order to obtain stable LB films, the influences of different parameters - type of amphiphile, surface pressure and pH - on the properties of mixed IgG/amphiphile monolayer, were investigated. Electrochemical properties of the engineered immunosensor have been measured by impedimetric spectroscopy. The immunosensor obtained exhibits a high sensitivity and a good specificity in a linear dynamic range from 200 to 1000 ng ml(-1).

Animals↗

ESPD: a pattern detection model underlying gene expression profiles.

MOTIVATION: DNA arrays permit rapid, large-scale screening for patterns of gene expression and simultaneously yield the expression levels of thousands of genes for samples. The number of samples is usually limited, and such datasets are very sparse in high-dimensional gene space. Furthermore, most of the genes collected may not necessarily be of interest and uncertainty about which genes are relevant makes it difficult to construct an informative gene space. Unsupervised empirical sample pattern discovery and informative genes identification of such sparse high-dimensional datasets present interesting but challenging problems. RESULTS: A new model called empirical sample pattern detection (ESPD) is proposed to delineate pattern quality with informative genes. By integrating statistical metrics, data mining and machine learning techniques, this model dynamically measures and manipulates the relationship between samples and genes while conducting an iterative detection of informative space and the empirical pattern. The performance of the proposed method with various array datasets is illustrated.

Algorithms↗

VizStruct: exploratory visualization for gene expression profiling.

MOTIVATION: DNA arrays provide a broad snapshot of the state of the cell by measuring the expression levels of thousands of genes simultaneously. Visualization techniques can enable the exploration and detection of patterns and relationships in a complex data set by presenting the data in a graphical format in which the key characteristics become more apparent. The dimensionality and size of array data sets however present significant challenges to visualization. The purpose of this study is to present an interactive approach for visualizing variations in gene expression profiles and to assess its usefulness for classifying samples. RESULTS: The first Fourier harmonic projection was used to map multi-dimensional gene expression data to two dimensions in an implementation called VizStruct. The visualization method was tested using the differentially expressed genes identified in eight separate gene expression data sets. The samples were classified using the oblique decision tree (OC1) algorithm to provide a procedure for visualization-driven classification. The classifiers were evaluated by the holdout and the cross-validation techniques. The proposed method was found to achieve high accuracy. AVAILABILITY: Detailed mathematical derivation of all mapping properties as well as figures in color can be found as supplementary on the web page http://www.cse.buffalo.edu/DBGROUP/bioinformatics/supplementary/vizstruct. All programs were written in Java and Matlab and software code is available by request from the first author.

Algorithms↗

Analysis of pharmacokinetics, pharmacodynamics, and pharmacogenomics data sets using VizStruct, a novel multidimensional visualization technique.

PURPOSE: Data visualization techniques for the pharmaceutical sciences have not been extensively investigated. The purpose of this study was to evaluate the usefulness of VizStruct, a multidimensional visualization tool, for applications in pharmacokinetics, pharmacodynamics, and pharmacogenomics. METHODS: The VizStruct tool uses the first harmonic of the discrete Fourier transform to map multidimensional data to two dimensions for visualization. The mapping was used to visualize several published pharmacokinetic, pharmacodynamic, and pharmacogenomic data sets. The VizStruct approach was evaluated using simulated population pharmacokinetics data sets, the data from Dalen and colleagues (Clin. PharmacoL Ther. 63:444-452, 1998) on the kinetics of nortriptyline and its 10-hydroxynortriptyline metabolite in subjects with differing number of copies of the CYP2D6, and the gene expression profiling data of Bohen and colleagues (Proc. Natl. Acad. Sci. USA 100:1926-1930, 2003) on follicular lymphoma patients responsive and nonresponsive to rituximab. RESULTS: The VizStruct mapping preserves the key characteristics of multidimensional data in two dimensions in a manner that facilitates visualization. The mapping is computationally efficient and can be used for cluster detection and class prediction in pharmaceutical data sets. The VizStruct visualization succinctly summarized the salient similarities and differences in the nortriptyline and 10-hydroxynortriptyline pharmacokinetic profiles in subjects with increasing number of CYP2D6 gene copies. In the simulated population pharmacokinetic data sets, it was capable of discriminating the subtle differences between pharmacokinetic profiles derived from 1- and 2-compartment models with the same area under the curve. The two-dimensional VizStruct mapping computed from a subset of 102 informative genes from the Bohen and colleagues data set effectively separated the rituximab responder, rituximab nonresponder, and control subject groups. CONCLUSIONS: The VizStruct approach is a computationally efficient and effective approach for visualizing complex, multidimensional data sets. It could have many useful applications in the pharmaceutical sciences.

Algorithms↗

Fourier harmonic approach for visualizing temporal patterns of gene expression data.

DNA microarray technology provides a broad snapshot of the state of the cell by measuring the expression levels of thousands of genes simultaneously. Visualization techniques can enable the exploration and detection of patterns and relationships in a complex dataset by presenting the data in a graphical format in which the key characteristics become more apparent. The purpose of this study is to present an interactive visualization technique conveying the temporal patterns of gene expression data in a form intuitive for non-specialized end-users. The first Fourier harmonic projection (FFHP) was introduced to translate the multi-dimensional time series data into a two dimensional scatter plot. The spatial relationship of the points reflect the structure of the original dataset and relationships among clusters become two dimensional. The proposed method was tested using two published, array-derived gene expression datasets. Our results demonstrate the effectiveness of the approach.

Algorithms↗

Mixed urease/amphiphile LB films and their application for biosensor development.

The optimal conditions for the formation of a stable mixed urease/octadecylamine (ODA) film at the air-water interface are determined. This film is efficiently transferred onto the hydrophobized surface of a pH-ISFET, and the features of the urea enzymatic field-effect transistor (ENFET) are determined: detection limit 0.2 mM, response time 15 s, and dynamic range 0-20 mM.

Amines↗