The development of a topic in a set of topic documents is constituted by a series of person interactions at a specific time and place. Knowing the interactions of the persons mentioned in these ...documents is helpful for readers to better comprehend the documents. In this paper, we propose a topic person interaction detection method called SPIRIT, which classifies the text segments in a set of topic documents that convey person interactions. We design the rich interactive tree structure to represent syntactic, context, and semantic information of text, and this structure is incorporated into a tree-based convolution kernel to identify interactive segments. Experiment results based on real world topics demonstrate that the proposed rich interactive tree structure effectively detects the topic person interactions and that our method outperforms many well-known relation extraction and protein-protein interaction methods.
Protein-protein interactions are critical determinants in biological systems. Engineered proteins binding to specific areas on protein surfaces could lead to therapeutics or diagnostics for treating ...diseases in humans. But designing epitope-specific protein-protein interactions with computational atomistic interaction free energy remains a difficult challenge. Here we show that, with the antibody-VEGF (vascular endothelial growth factor) interaction as a model system, the experimentally observed amino acid preferences in the antibody-antigen interface can be rationalized with 3-dimensional distributions of interacting atoms derived from the database of protein structures. Machine learning models established on the rationalization can be generalized to design amino acid preferences in antibody-antigen interfaces, for which the experimental validations are tractable with current high throughput synthetic antibody display technologies. Leave-one-out cross validation on the benchmark system yielded the accuracy, precision, recall (sensitivity) and specificity of the overall binary predictions to be 0.69, 0.45, 0.63, and 0.71 respectively, and the overall Matthews correlation coefficient of the 20 amino acid types in the 24 interface CDR positions was 0.312. The structure-based computational antibody design methodology was further tested with other antibodies binding to VEGF. The results indicate that the methodology could provide alternatives to the current antibody technologies based on animal immune systems in engineering therapeutic and diagnostic antibodies against predetermined antigen epitopes.
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Biomedical named entity recognition (Bio-NER) is a challenging problem because, in general, biomedical named entities of the same category (e.g., proteins and genes) do not follow one standard ...nomenclature. They have many irregularities and sometimes appear in ambiguous contexts. In recent years, machine-learning (ML) approaches have become increasingly common and now represent the cutting edge of Bio-NER technology. This paper addresses three problems faced by ML-based Bio-NER systems. First, most ML approaches usually employ singleton features that comprise one linguistic property (e.g., the current word is capitalized) and at least one class tag (e.g., B-protein, the beginning of a protein name). However, such features may be insufficient in cases where multiple properties must be considered. Adding conjunction features that contain multiple properties can be beneficial, but it would be infeasible to include all conjunction features in an NER model since memory resources are limited and some features are ineffective. To resolve the problem, we use a sequential forward search algorithm to select an effective set of features. Second, variations in the numerical parts of biomedical terms (e.g., "2" in the biomedical term IL2) cause data sparseness and generate many redundant features. In this case, we apply numerical normalization, which solves the problem by replacing all numerals in a term with one representative numeral to help classify named entities. Third, the assignment of NE tags does not depend solely on the target word's closest neighbors, but may depend on words outside the context window (e.g., a context window of five consists of the current word plus two preceding and two subsequent words). We use global patterns generated by the Smith-Waterman local alignment algorithm to identify such structures and modify the results of our ML-based tagger. This is called pattern-based post-processing.
To develop our ML-based Bio-NER system, we employ conditional random fields, which have performed effectively in several well-known tasks, as our underlying ML model. Adding selected conjunction features, applying numerical normalization, and employing pattern-based post-processing improve the F-scores by 1.67%, 1.04%, and 0.57%, respectively. The combined increase of 3.28% yields a total score of 72.98%, which is better than the baseline system that only uses singleton features.
We demonstrate the benefits of using the sequential forward search algorithm to select effective conjunction feature groups. In addition, we show that numerical normalization can effectively reduce the number of redundant and unseen features. Furthermore, the Smith-Waterman local alignment algorithm can help ML-based Bio-NER deal with difficult cases that need longer context windows.
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Protein and peptide identification and quantitation are essential tasks in proteomics research and involve a series of steps in analyzing mass spectrometry data. Trans-Proteomic Pipeline (TPP) ...provides a wide range of useful tools through its web interfaces for analyses such as sequence database search, statistical validation, and quantitation. To utilize the powerful functionality of TPP without the need for manual intervention to launch each step, we developed a software tool, called WinProphet, to create and automatically execute a pipeline for proteomic analyses. It seamlessly integrates with TPP and other external command-line programs, supporting various functionalities, including database search for protein and peptide identification, spectral library construction and search, data-independent acquisition (DIA) data analysis, and isobaric labeling and label-free quantitation. WinProphet is a standalone, installation-free tool with graphical interfaces for users to configure, manage, and automatically execute pipelines. The constructed pipelines can be exported as XML files with all of the parameter settings for reusability and portability. The executable files, user manual, and sample data sets of WinProphet are freely available at http://ms.iis.sinica.edu.tw/COmics/Software_WinProphet.html.
Identifying the interactions between chemical compounds and genes from biomedical literatures is one of the frequently discussed topics of text mining in the life science field. In this paper, we ...describe Linguistic Pattern-Aware Dependency Tree Kernel, a linguistic interaction pattern learning method developed for CHEMPROT task-BioCreative VI, to capture chemical-protein interaction (CPI) patterns within biomedical literatures. We also introduce a framework to integrate these linguistic patterns with smooth partial tree kernel to extract the CPIs. This new method of feature representation models aspects of linguistic probability in geometric representation, which not only optimizes the sufficiency of feature dimension for classification, but also defines features as interpretable contexts rather than long vectors of numbers. In order to test the robustness and efficiency of our system in identifying different kinds of biological interactions, we evaluated our framework on three separate data sets, i.e. CHEMPROT corpus, Chemical-Disease Relation corpus and Protein-Protein Interaction corpus. Corresponding experiment results demonstrate that our method is effective and outperforms several compared systems for each data set.
Abstract
In this research, we explored various state-of-the-art biomedical-specific pre-trained Bidirectional Encoder Representations from Transformers (BERT) models for the National Library of ...Medicine - Chemistry (NLM CHEM) and LitCovid tracks in the BioCreative VII Challenge, and propose a BERT-based ensemble learning approach to integrate the advantages of various models to improve the system’s performance. The experimental results of the NLM-CHEM track demonstrate that our method can achieve remarkable performance, with F1-scores of 85% and 91.8% in strict and approximate evaluations, respectively. Moreover, the proposed Medical Subject Headings identifier (MeSH ID) normalization algorithm is effective in entity normalization, which achieved a F1-score of about 80% in both strict and approximate evaluations. For the LitCovid track, the proposed method is also effective in detecting topics in the Coronavirus disease 2019 (COVID-19) literature, which outperformed the compared methods and achieve state-of-the-art performance in the LitCovid corpus.
Database URL: https://www.ncbi.nlm.nih.gov/research/coronavirus/.
Efficient and accurate quantitation of metabolites from LC-MS data has become an important topic. Here we present an automated tool, called iMet-Q (intelligent Metabolomic Quantitation), for ...label-free metabolomics quantitation from high-throughput MS1 data. By performing peak detection and peak alignment, iMet-Q provides a summary of quantitation results and reports ion abundance at both replicate level and sample level. Furthermore, it gives the charge states and isotope ratios of detected metabolite peaks to facilitate metabolite identification. An in-house standard mixture and a public Arabidopsis metabolome data set were analyzed by iMet-Q. Three public quantitation tools, including XCMS, MetAlign, and MZmine 2, were used for performance comparison. From the mixture data set, seven standard metabolites were detected by the four quantitation tools, for which iMet-Q had a smaller quantitation error of 12% in both profile and centroid data sets. Our tool also correctly determined the charge states of seven standard metabolites. By searching the mass values for those standard metabolites against Human Metabolome Database, we obtained a total of 183 metabolite candidates. With the isotope ratios calculated by iMet-Q, 49% (89 out of 183) metabolite candidates were filtered out. From the public Arabidopsis data set reported with two internal standards and 167 elucidated metabolites, iMet-Q detected all of the peaks corresponding to the internal standards and 167 metabolites. Meanwhile, our tool had small abundance variation (≤ 0.19) when quantifying the two internal standards and had higher abundance correlation (≥ 0.92) when quantifying the 167 metabolites. iMet-Q provides user-friendly interfaces and is publicly available for download at http://ms.iis.sinica.edu.tw/comics/Software_iMet-Q.html.
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Extractive text or speech summarization manages to select a set of salient sentences from an original document and concatenate them to form a summary, enabling users to better browse through and ...understand the content of the document. A recent stream of research on extractive summarization is to employ the language modeling (LM) approach for important sentence selection, which has proven to be effective for performing speech summarization in an unsupervised fashion. However, one of the major challenges facing the LM approach is how to formulate the sentence models and accurately estimate their parameters for each sentence in the document to be summarized. In view of this, our work in this paper explores a novel use of recurrent neural network language modeling (RNNLM) framework for extractive broadcast news summarization. On top of such a framework, the deduced sentence models are able to render not only word usage cues but also long-span structural information of word co-occurrence relationships within broadcast news documents, getting around the need for the strict bag-of-words assumption. Furthermore, different model complexities and combinations are extensively analyzed and compared. Experimental results demonstrate the performance merits of our summarization methods when compared to several well-studied state-of-the-art unsupervised methods.
MAGIC-web is the first web server, to the best of our knowledge, that performs both untargeted and targeted analyses of mass spectrometry-based glycoproteomics data for site-specific N-linked ...glycoprotein identification. The first two modules, MAGIC and MAGIC+, are designed for untargeted and targeted analysis, respectively. MAGIC is implemented with our previously proposed novel Y1-ion pattern matching method, which adequately detects Y1- and Y0-ion without prior information of proteins and glycans, and then generates in silico MS(2) spectra that serve as input to a database search engine (e.g. Mascot) to search against a large-scale protein sequence database. On top of that, the newly implemented MAGIC+ allows users to determine glycopeptide sequences using their own protein sequence file. The third module, Reports Integrator, provides the service of combining protein identification results from Mascot and glycan-related information from MAGIC-web to generate a complete site-specific protein-glycan summary report. The last module, Glycan Search, is designed for the users who are interested in finding possible glycan structures with specific numbers and types of monosaccharides. The results from MAGIC, MAGIC+ and Reports Integrator can be downloaded via provided links whereas the annotated spectra and glycan structures can be visualized in the browser. MAGIC-web is accessible from http://ms.iis.sinica.edu.tw/MAGIC-web/index.html.
Non-covalent protein-carbohydrate interactions mediate molecular targeting in many biological processes. Prediction of non-covalent carbohydrate binding sites on protein surfaces not only provides ...insights into the functions of the query proteins; information on key carbohydrate-binding residues could suggest site-directed mutagenesis experiments, design therapeutics targeting carbohydrate-binding proteins, and provide guidance in engineering protein-carbohydrate interactions. In this work, we show that non-covalent carbohydrate binding sites on protein surfaces can be predicted with relatively high accuracy when the query protein structures are known. The prediction capabilities were based on a novel encoding scheme of the three-dimensional probability density maps describing the distributions of 36 non-covalent interacting atom types around protein surfaces. One machine learning model was trained for each of the 30 protein atom types. The machine learning algorithms predicted tentative carbohydrate binding sites on query proteins by recognizing the characteristic interacting atom distribution patterns specific for carbohydrate binding sites from known protein structures. The prediction results for all protein atom types were integrated into surface patches as tentative carbohydrate binding sites based on normalized prediction confidence level. The prediction capabilities of the predictors were benchmarked by a 10-fold cross validation on 497 non-redundant proteins with known carbohydrate binding sites. The predictors were further tested on an independent test set with 108 proteins. The residue-based Matthews correlation coefficient (MCC) for the independent test was 0.45, with prediction precision and sensitivity (or recall) of 0.45 and 0.49 respectively. In addition, 111 unbound carbohydrate-binding protein structures for which the structures were determined in the absence of the carbohydrate ligands were predicted with the trained predictors. The overall prediction MCC was 0.49. Independent tests on anti-carbohydrate antibodies showed that the carbohydrate antigen binding sites were predicted with comparable accuracy. These results demonstrate that the predictors are among the best in carbohydrate binding site predictions to date.
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