Biomolecular Event Extraction using Natural Language Processing

Biomedical research and discoveries are communicated through scholarly publications and this literature is voluminous, rich in scientific text and growing exponentially by the day. Biomedical journals publish nearly three thousand research articles daily, making literature search a challenging proposition for researchers. Biomolecular events involve genes, proteins, metabolites, and enzymes that provide invaluable insights into biological processes and explain the physiological functional mechanisms. Text mining (TM) or extraction of such events automatically from big data is the only quick and viable solution to gather any useful information. Such events extracted from biological literature have a broad range of applications like database curation, ontology construction, semantic web search and interactive systems. However, automatic extraction has its challenges on account of ambiguity and the diverse nature of natural language and associated linguistic occurrences like speculations, negations etc., which commonly exist in biomedical texts and lead to erroneous elucidation. In the last decade, many strategies have been proposed in this field, using different paradigms like Biomedical natural language processing (BioNLP), machine learning and deep learning. Also, new parallel computing architectures like graphical processing units (GPU) have emerged as possible candidates to accelerate the event extraction pipeline. This paper reviews and provides a summarization of the key approaches in complex biomolecular big data event extraction tasks and recommends a balanced architecture in terms of accuracy, speed, computational cost, and memory usage towards developing a robust GPU-accelerated BioNLP system

Extracting Biomolecular Interactions Using Semantic Parsing of Biomedical Text

We advance the state of the art in biomolecular interaction extraction with three contributions: (i) We show that deep, Abstract Meaning Representations (AMR) significantly improve the accuracy of a biomolecular interaction extraction system when compared to a baseline that relies solely on surface- and syntax-based features; (ii) In contrast with previous approaches that infer relations on a sentence-by-sentence basis, we expand our framework to enable consistent predictions over sets of sentences (documents); (iii) We further modify and expand a graph kernel learning framework to enable concurrent exploitation of automatically induced AMR (semantic) and dependency structure (syntactic) representations. Our experiments show that our approach yields interaction extraction systems that are more robust in environments where there is a significant mismatch between training and test conditions.Comment: Appearing in Proceedings of the Thirtieth AAAI Conference on Artificial Intelligence (AAAI-16

Biomedical Event Extraction as Sequence Labeling

We introduce Biomedical Event Extraction as Sequence Labeling (BeeSL), a joint end-to-end neural information extraction model. BeeSL recasts the task as sequence labeling, taking advantage of a multi-label aware encoding strategy and jointly modeling the intermediate tasks via multi-task learning. BeeSL is fast, accurate, end-to-end, and unlike current methods does not require any external knowledge base or preprocessing tools. BeeSL outperforms the current best system (Li et al., 2019) on the Genia 2011 benchmark by 1.57% absolute F1 score reaching 60.22% F1, establishing a new state of the art for the task. Importantly, we also provide first results on biomedical event extraction without gold entity information. Empirical results show that BeeSL's speed and accuracy makes it a viable approach for large-scale real-world scenarios

Biomedical Event Extraction with Machine Learning

Biomedical natural language processing (BioNLP) is a subfield of natural language processing, an area of computational linguistics concerned with developing programs that work with natural language: written texts and speech. Biomedical relation extraction concerns the detection of semantic relations such as protein--protein interactions (PPI) from scientific texts. The aim is to enhance information retrieval by detecting relations between concepts, not just individual concepts as with a keyword search. In recent years, events have been proposed as a more detailed alternative for simple pairwise PPI relations. Events provide a systematic, structural representation for annotating the content of natural language texts. Events are characterized by annotated trigger words, directed and typed arguments and the ability to nest other events. For example, the sentence ``Protein A causes protein B to bind protein C&#39;&#39; can be annotated with the nested event structure CAUSE(A, BIND(B, C)). Converted to such formal representations, the information of natural language texts can be used by computational applications. Biomedical event annotations were introduced by the BioInfer and GENIA corpora, and event extraction was popularized by the BioNLP&#39;09 Shared Task on Event Extraction. In this thesis we present a method for automated event extraction, implemented as the Turku Event Extraction System (TEES). A unified graph format is defined for representing event annotations and the problem of extracting complex event structures is decomposed into a number of independent classification tasks. These classification tasks are solved using SVM and RLS classifiers, utilizing rich feature representations built from full dependency parsing.&nbsp; Building on earlier work on pairwise relation extraction and using a generalized graph representation, the resulting TEES system is capable of detecting binary relations as well as complex event structures. We show that this event extraction system has good performance, reaching the first place in the BioNLP&#39;09 Shared Task on Event Extraction. Subsequently, TEES has achieved several first ranks in the BioNLP&#39;11 and BioNLP&#39;13 Shared Tasks, as well as shown competitive performance in the binary relation Drug-Drug Interaction Extraction 2011 and 2013 shared tasks. The Turku Event Extraction System is published as a freely available open-source project, documenting the research in detail as well as making the method available for practical applications. In particular, in this thesis we describe the application of the event extraction method to PubMed-scale text mining, showing how the developed approach not only shows good performance, but is generalizable and applicable to large-scale real-world text mining projects. Finally, we discuss related literature, summarize the contributions of the work and present some thoughts on future directions for biomedical event extraction. This thesis includes and builds on six original research publications. The first of these introduces the analysis of dependency parses that leads to development of TEES. The entries in the three BioNLP Shared Tasks, as well as in the DDIExtraction 2011 task are covered in four publications, and the sixth one demonstrates the application of the system to PubMed-scale text mining.</p

Biomedical Event Extraction with Machine Learning

Biomedical natural language processing (BioNLP) is a subfield of natural language processing, an area of computational linguistics concerned with developing programs that work with natural language: written texts and speech. Biomedical relation extraction concerns the detection of semantic relations such as protein-protein interactions (PPI) from scientific texts. The aim is to enhance information retrieval by detecting relations between concepts, not just individual concepts as with a keyword search. In recent years, events have been proposed as a more detailed alternative for simple pairwise PPI relations. Events provide a systematic, structural representation for annotating the content of natural language texts. Events are characterized by annotated trigger words, directed and typed arguments and the ability to nest other events. For example, the sentence “Protein A causes protein B to bind protein C” can be annotated with the nested event structure CAUSE(A, BIND(B, C)). Converted to such formal representations, the information of natural language texts can be used by computational applications. Biomedical event annotations were introduced by the BioInfer and GENIA corpora, and event extraction was popularized by the BioNLP'09 Shared Task on Event Extraction. In this thesis we present a method for automated event extraction, implemented as the Turku Event Extraction System (TEES). A unified graph format is defined for representing event annotations and the problem of extracting complex event structures is decomposed into a number of independent classification tasks. These classification tasks are solved using SVM and RLS classifiers, utilizing rich feature representations built from full dependency parsing. Building on earlier work on pairwise relation extraction and using a generalized graph representation, the resulting TEES system is capable of detecting binary relations as well as complex event structures. We show that this event extraction system has good performance, reaching the first place in the BioNLP'09 Shared Task on Event Extraction. Subsequently, TEES has achieved several first ranks in the BioNLP'11 and BioNLP'13 Shared Tasks, as well as shown competitive performance in the binary relation Drug-Drug Interaction Extraction 2011 and 2013 shared tasks. The Turku Event Extraction System is published as a freely available open-source project, documenting the research in detail as well as making the method available for practical applications. In particular, in this thesis we describe the application of the event extraction method to PubMed-scale text mining, showing how the developed approach not only shows good performance, but is generalizable and applicable to large-scale real-world text mining projects. Finally, we discuss related literature, summarize the contributions of the work and present some thoughts on future directions for biomedical event extraction. This thesis includes and builds on six original research publications. The first of these introduces the analysis of dependency parses that leads to development of TEES. The entries in the three BioNLP Shared Tasks, as well as in the DDIExtraction 2011 task are covered in four publications, and the sixth one demonstrates the application of the system to PubMed-scale text mining.Siirretty Doriast

Accurate Prediction Methods on Biomolecular Data

With the recent advancements in sequencing technologies, molecular biologists are producing ever-increasing amounts of biomolecular data. Extracting useful information from these massive data sets requires efficient and effective data mining and machine learning methods. In this dissertation, we explore the use of supervised machine learning (ML) to solve some challenging classification problems in molecular biology.First, we devise an ML model for classifying cancer types from very sparse somatic point mutation data. Accumulation of mutation and epigenetic modifications in somatic cells results in various cancer. For this purpose, we propose a method called mClass for efficient feature (gene) ranking that uses clustering, normalized mutual information and logistic regression. We show that somatic mutation data has sufficient discriminative power for cancer type classification.Next, we address the problem of gene essentiality prediction in microbes. Essential genes are significant to identify since their function is vital for the survival of the organism. Our proposed deep learning architecture called DeeplyEssential exclusively uses features extracted from the primary sequence of genes and their corresponding proteins, to maximize the utility and practicality of the tool. DeeplyEssential achieved state-of-the-art performance over previously proposed methods as well as expose and study a hidden performance bias affected previous models.Finally, we consider the problem of predicting the enhancer regions in the human genome from chromatin data. Enhancers contribute to the transcription of target genes. We propose a convolutional neural network framework named Epi2En that takes advantage of epigenetic ChIP-seq data. Epi2En's classification performance is not only very strong on cross-validation experiments, but also when testing across different cell-lines

Machine Learning Models for Deciphering Regulatory Mechanisms and Morphological Variations in Cancer

The exponential growth of multi-omics biological datasets is resulting in an emerging paradigm shift in fundamental biological research. In recent years, imaging and transcriptomics datasets are increasingly incorporated into biological studies, pushing biology further into the domain of data-intensive-sciences. New approaches and tools from statistics, computer science, and data engineering are profoundly influencing biological research. Harnessing this ever-growing deluge of multi-omics biological data requires the development of novel and creative computational approaches. In parallel, fundamental research in data sciences and Artificial Intelligence (AI) has advanced tremendously, allowing the scientific community to generate a massive amount of knowledge from data. Advances in Deep Learning (DL), in particular, are transforming many branches of engineering, science, and technology. Several of these methodologies have already been adapted for harnessing biological datasets; however, there is still a need to further adapt and tailor these techniques to new and emerging technologies. In this dissertation, we present computational algorithms and tools that we have developed to study gene-regulation and cellular morphology in cancer. The models and platforms that we have developed are general and widely applicable to several problems relating to dysregulation of gene expression in diseases. Our pipelines and software packages are disseminated in public repositories for larger scientific community use. This dissertation is organized in three main projects. In the first project, we present Causal Inference Engine (CIE), an integrated platform for the identification and interpretation of active regulators of transcriptional response. The platform offers visualization tools and pathway enrichment analysis to map predicted regulators to Reactome pathways. We provide a parallelized R-package for fast and flexible directional enrichment analysis to run the inference on custom regulatory networks. Next, we designed and developed MODEX, a fully automated text-mining system to extract and annotate causal regulatory interaction between Transcription Factors (TFs) and genes from the biomedical literature. MODEX uses putative TF-gene interactions derived from high-throughput ChIP-Seq or other experiments and seeks to collect evidence and meta-data in the biomedical literature to validate and annotate the interactions. MODEX is a complementary platform to CIE that provides auxiliary information on CIE inferred interactions by mining the literature. In the second project, we present a Convolutional Neural Network (CNN) classifier to perform a pan-cancer analysis of tumor morphology, and predict mutations in key genes. The main challenges were to determine morphological features underlying a genetic status and assess whether these features were common in other cancer types. We trained an Inception-v3 based model to predict TP53 mutation in five cancer types with the highest rate of TP53 mutations. We also performed a cross-classification analysis to assess shared morphological features across multiple cancer types. Further, we applied a similar methodology to classify HER2 status in breast cancer and predict response to treatment in HER2 positive samples. For this study, our training slides were manually annotated by expert pathologists to highlight Regions of Interest (ROIs) associated with HER2+/- tumor microenvironment. Our results indicated that there are strong morphological features associated with each tumor type. Moreover, our predictions highly agree with manual annotations in the test set, indicating the feasibility of our approach in devising an image-based diagnostic tool for HER2 status and treatment response prediction. We have validated our model using samples from an independent cohort, which demonstrates the generalizability of our approach. Finally, in the third project, we present an approach to use spatial transcriptomics data to predict spatially-resolved active gene regulatory mechanisms in tissues. Using spatial transcriptomics, we identified tissue regions with differentially expressed genes and applied our CIE methodology to predict active TFs that can potentially regulate the marker genes in the region. This project bridged the gap between inference of active regulators using molecular data and morphological studies using images. The results demonstrate a significant local pattern in TF activity across the tissue, indicating differential spatial-regulation in tissues. The results suggest that the integrative analysis of spatial transcriptomics data with CIE can capture discriminant features and identify localized TF-target links in the tissue