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Extracting glycan motifs using a biochemicallyweighted kernel.

ABSTRACT: Carbohydrates, or glycans, are one of the most abundant and structurally diverse biopolymers constitute the third major class of biomolecules, following DNA and proteins. However, the study of carbohydrate sugar chains has lagged behind compared to that of DNA and proteins, mainly due to their inherent structural complexity. However, their analysis is important because they serve various important roles in biological processes, including signaling transduction and cellular recognition. In order to glean some light into glycan function based on carbohydrate structure, kernel methods have been developed in the past, in particular to extract potential glycan biomarkers by classifying glycan structures found in different tissue samples. The recently developed weighted qgram method (LK-method) exhibits good performance on glycan structure classification while having limitations in feature selection. That is, it was unable to extract biologically meaningful features from the data. Therefore, we propose a biochemicallyweighted tree kernel (BioLK-method) which is based on a glycan similarity matrix and also incorporates biochemical information of individual q-grams in constructing the kernel matrix. We further applied our new method for the classification and recognition of motifs on publicly available glycan data. Our novel tree kernel (BioLK-method) using a Support Vector Machine (SVM) is capable of detecting biologically important motifs accurately while LK-method failed to do so. It was tested on three glycan data sets from the Consortium for Functional Glycomics (CFG) and Kyoto Encyclopedia of Genes and Genomes (KEGG) GLYCAN and showed that the results are consistent with the literature. The newly developed BioLK-method also maintains comparable classification performance with the LK-method. Our results obtained here indicate that the incorporation of biochemical information of q-grams further shows the flexibility and capability of the novel kernel in feature extraction, which may aid in the prediction of glycan biomarkers.

SUBMITTER: Jiang H

PROVIDER: S-EPMC3280441 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Extracting glycan motifs using a biochemicallyweighted kernel.

Jiang Hao H Aoki-Kinoshita Kiyoko F KF Ching Wai-Ki WK

Bioinformation 20111221 8

Carbohydrates, or glycans, are one of the most abundant and structurally diverse biopolymers constitute the third major class of biomolecules, following DNA and proteins. However, the study of carbohydrate sugar chains has lagged behind compared to that of DNA and proteins, mainly due to their inherent structural complexity. However, their analysis is important because they serve various important roles in biological processes, including signaling transduction and cellular recognition. In order ...[more]

PMID: 22347783

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Project description:BACKGROUND:Glycans are complex sugar chains, crucial to many biological processes. By participating in binding interactions with proteins, glycans often play key roles in host-pathogen interactions. The specificities of glycan-binding proteins, such as lectins and antibodies, are governed by motifs within larger glycan structures, and improved characterisations of these determinants would aid research into human diseases. Identification of motifs has previously been approached as a frequent subtree mining problem, and we extend these approaches with a glycan notation that allows recognition of terminal motifs. RESULTS:In this work, we customised a frequent subtree mining approach by altering the glycan notation to include information on terminal connections. This allows specific identification of terminal residues as potential motifs, better capturing the complexity of glycan-binding interactions. We achieved this by including additional nodes in a graph representation of the glycan structure to indicate the presence or absence of a linkage at particular backbone carbon positions. Combining this frequent subtree mining approach with a state-of-the-art feature selection algorithm termed minimum-redundancy, maximum-relevance (mRMR), we have generated a classification pipeline that is trained on data from a glycan microarray. When applied to a set of commonly used lectins, the identified motifs were consistent with known binding determinants. Furthermore, logistic regression classifiers trained using these motifs performed well across most lectins examined, with a median AUC value of 0.89. CONCLUSIONS:We present here a new subtree mining approach for the classification of glycan binding and identification of potential binding motifs. The Carbohydrate Classification Accounting for Restricted Linkages (CCARL) method will assist in the interpretation of glycan microarray experiments and will aid in the discovery of novel binding motifs for further experimental characterisation.

Project description:Approaches studying the dynamics of resting-state functional magnetic resonance imaging (rs-fMRI) activity often focus on time-resolved functional connectivity (tr-FC). While many approaches have been proposed, these typically focus on linear approaches like computing the linear correlation at a timestep or within a window. In this work, we propose to use a generative non-linear deep learning model, a disentangled variational autoencoder (DSVAE), that factorizes out window-specific (context) information from timestep-specific (local) information. This has the advantage of allowing our model to capture differences at multiple temporal scales. For the timestep-specific scale, which has higher temporal precision, we find significant differences between schizophrenia patients and control subjects in their temporal step distance through our model's latent space. We also find that window-specific embeddings, or as we refer to them, context embeddings, more accurately separate windows from schizophrenia patients and control subjects than the standard tr-FC approach. Moreover, we find that for individuals with schizophrenia, our model's context embedding space is significantly correlated with both age and symptom severity. Interestingly, patients appear to spend more time in three clusters, one closer to controls which shows increased visual-sensorimotor, cerebellar-subcortical, and reduced cerebellar-sensorimotor functional network connectivity (FNC), an intermediate station showing increased subcortical-sensorimotor FNC, and one that shows decreased visual-sensorimotor, decreased subcortical-sensorimotor, and increased visual-subcortical domains. We verify that our model captures features that are complementary to - but not the same as - standard tr-FC features. Our model can thus help broaden the neuroimaging toolset in analyzing fMRI dynamics and shows potential as an approach for finding psychiatric links that are more sensitive to individual and group characteristics.

Project description:BackgroundEnzymatic and chemical reactions are key for understanding biological processes in cells. Curated databases of chemical reactions exist but these databases struggle to keep up with the exponential growth of the biomedical literature. Conventional text mining pipelines provide tools to automatically extract entities and relationships from the scientific literature, and partially replace expert curation, but such machine learning frameworks often require a large amount of labeled training data and thus lack scalability for both larger document corpora and new relationship types.ResultsWe developed an application of Snorkel, a weakly supervised learning framework, for extracting chemical reaction relationships from biomedical literature abstracts. For this work, we defined a chemical reaction relationship as the transformation of chemical A to chemical B. We built and evaluated our system on small annotated sets of chemical reaction relationships from two corpora: curated bacteria-related abstracts from the MetaCyc database (MetaCyc_Corpus) and a more general set of abstracts annotated with MeSH (Medical Subject Headings) term Bacteria (Bacteria_Corpus; a superset of MetaCyc_Corpus). For the MetaCyc_Corpus, we obtained 84% precision and 41% recall (55% F1 score). Extending to the more general Bacteria_Corpus decreased precision to 62% with only a four-point drop in recall to 37% (46% F1 score). Overall, the Bacteria_Corpus contained two orders of magnitude more candidate chemical reaction relationships (nine million candidates vs 68,0000 candidates) and had a larger class imbalance (2.5% positives vs 5% positives) as compared to the MetaCyc_Corpus. In total, we extracted 6871 chemical reaction relationships from nine million candidates in the Bacteria_Corpus.ConclusionsWith this work, we built a database of chemical reaction relationships from almost 900,000 scientific abstracts without a large training set of labeled annotations. Further, we showed the generalizability of our initial application built on MetaCyc documents enriched with chemical reactions to a general set of articles related to bacteria.

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Extracting glycan motifs using a biochemicallyweighted kernel.

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Extracting glycan motifs using a biochemicallyweighted kernel.

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