Dataset Information

Exploring Integrative Analysis Using the BioMedical Evidence Graph.

ABSTRACT:

Purpose

The analysis of cancer biology data involves extremely heterogeneous data sets, including information from RNA sequencing, genome-wide copy number, DNA methylation data reporting on epigenetic regulation, somatic mutations from whole-exome or whole-genome analyses, pathology estimates from imaging sections or subtyping, drug response or other treatment outcomes, and various other clinical and phenotypic measurements. Bringing these different resources into a common framework, with a data model that allows for complex relationships as well as dense vectors of features, will unlock integrated data set analysis.

Methods

We introduce the BioMedical Evidence Graph (BMEG), a graph database and query engine for discovery and analysis of cancer biology. The BMEG is unique from other biologic data graphs in that sample-level molecular and clinical information is connected to reference knowledge bases. It combines gene expression and mutation data with drug-response experiments, pathway information databases, and literature-derived associations.

Results

The construction of the BMEG has resulted in a graph containing > 41 million vertices and 57 million edges. The BMEG system provides a graph query-based application programming interface to enable analysis, with client code available for Python, Javascript, and R, and a server online at bmeg.io. Using this system, we have demonstrated several forms of cross-data set analysis to show the utility of the system.

Conclusion

The BMEG is an evolving resource dedicated to enabling integrative analysis. We have demonstrated queries on the system that illustrate mutation significance analysis, drug-response machine learning, patient-level knowledge-base queries, and pathway level analysis. We have compared the resulting graph to other available integrated graph systems and demonstrated the former is unique in the scale of the graph and the type of data it makes available.

SUBMITTER: Struck A

PROVIDER: S-EPMC7049249 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Exploring Integrative Analysis Using the BioMedical Evidence Graph.

Struck Adam A Walsh Brian B Buchanan Alexander A Lee Jordan A JA Spangler Ryan R Stuart Joshua M JM Ellrott Kyle K

JCO clinical cancer informatics 20200201

<h4>Purpose</h4>The analysis of cancer biology data involves extremely heterogeneous data sets, including information from RNA sequencing, genome-wide copy number, DNA methylation data reporting on epigenetic regulation, somatic mutations from whole-exome or whole-genome analyses, pathology estimates from imaging sections or subtyping, drug response or other treatment outcomes, and various other clinical and phenotypic measurements. Bringing these different resources into a common framework, wit ...[more]

PMID: 32097025

Similar Datasets

Project description:Advances in machine learning and deep learning methods, together with the increasing availability of large-scale pharmacological, genomic, and chemical datasets, have created opportunities for identifying potentially useful relationships within biochemical networks. Knowledge embedding models have been found to have value in detecting knowledge-based correlations among entities, but little effort has been made to apply them to networks of biochemical entities. This is because such networks tend to be unbalanced and sparse, and knowledge embedding models do not work well on them. However, to some extent, the shortcomings of knowledge embedding models can be compensated for if they are used in association with graph embedding. In this paper, we combine knowledge embedding and graph embedding to represent biochemical entities and their relations as dense and low-dimensional vectors. We build a cascade learning framework which incorporates semantic features from the knowledge embedding model, and graph features from the graph embedding model, to score the probability of linking. The proposed method performs noticeably better than the models with which it is compared. It predicted links and entities with an accuracy of 93%, and its average hits@10 score has an average of 8.6% absolute improvement compared with original knowledge embedding model, 1.1% to 9.7% absolute improvement compared with other knowledge and graph embedding algorithm. In addition, we designed a meta-path algorithm to detect path relations in the biomedical network. Case studies further verify the value of the proposed model in finding potential relationships between diseases, drugs, genes, treatments, etc. Amongst the findings of the proposed model are the suggestion that VDR (vitamin D receptor) may be linked to prostate cancer. This is backed by evidence from medical databases and published research, supporting the suggestion that our proposed model could be of value to biomedical researchers.

Project description:Biomedical semantic indexing is a very useful support tool for human curators in their efforts for indexing and cataloging the biomedical literature.The aim of this study was to describe a system to automatically assign Medical Subject Headings (MeSH) to biomedical articles from MEDLINE.Our approach relies on the assumption that similar documents should be classified by similar MeSH terms. Although previous work has already exploited the document similarity by using a k-nearest neighbors algorithm, we represent documents as document vectors by search engine indexing and then compute the similarity between documents using cosine similarity. Once the most similar documents for a given input document are retrieved, we rank their MeSH terms to choose the most suitable set for the input document. To do this, we define a scoring function that takes into account the frequency of the term into the set of retrieved documents and the similarity between the input document and each retrieved document. In addition, we implement guidelines proposed by human curators to annotate MEDLINE articles; in particular, the heuristic that says if 3 MeSH terms are proposed to classify an article and they share the same ancestor, they should be replaced by this ancestor. The representation of the MeSH thesaurus as a graph database allows us to employ graph search algorithms to quickly and easily capture hierarchical relationships such as the lowest common ancestor between terms.Our experiments show promising results with an F1 of 69% on the test dataset.To the best of our knowledge, this is the first work that combines search and graph database technologies for the task of biomedical semantic indexing. Due to its horizontal scalability, ElasticSearch becomes a real solution to index large collections of documents (such as the bibliographic database MEDLINE). Moreover, the use of graph search algorithms for accessing MeSH information could provide a support tool for cataloging MEDLINE abstracts in real time.

Project description:BACKGROUND:Combination therapy plays an important role in the effective treatment of malignant neoplasms and precision medicine. Numerous clinical studies have been carried out to investigate combination drug therapies. Automated knowledge discovery of these combinations and their graphic representation in knowledge graphs will enable pattern recognition and identification of drug combinations used to treat a specific type of cancer, improve drug efficacy and treatment of human disorders. OBJECTIVE:This paper aims to develop an automated, visual approach to discover knowledge about combination therapies from biomedical literature, especially from those studies with high-level evidence such as clinical trial reports and clinical practice guidelines. METHODS:Based on semantic predications, which consist of a triple structure of subject-predicate-object (SPO), we proposed an automated algorithm to discover knowledge of combination drug therapies using the following rules: 1) two or more semantic predications (S1-P-O and Si-P-O, i = 2, 3…) can be extracted from one conclusive claim (sentence) in the abstract of a given publication, and 2) these predications have an identical predicate (that closely relates to human disease treatment, eg, "treat") and object (eg, disease name) but different subjects (eg, drug names). A customized knowledge graph organizes and visualizes these combinations, improving the traditional semantic triples. After automatic filtering of broad concepts such as "pharmacologic actions" and generic disease names, a set of combination drug therapies were identified and characterized through manual interpretation. RESULTS:We retrieved 22,263 clinical trial reports and 31 clinical practice guidelines from PubMed abstracts by searching "antineoplastic agents" for drug restriction (published between Jan 2009 and Oct 2019). There were 15,603 conclusive claims locally parsed using the search terms "conclusion*" and "conclude*" ready for semantic predications extraction by SemRep, and 325 candidate groups of semantic predications about combined medications were automatically discovered within 316 conclusive claims. Based on manual analysis, we determined that 255/316 claims (78.46%) were accurately identified as describing combination therapies and adopted these to construct the customized knowledge graph. We also identified two categories (and 4 subcategories) to characterize the inaccurate results: limitations of SemRep and limitations of proposal. We further learned the predominant patterns of drug combinations based on mechanism of action for new combined medication studies and discovered 4 obvious markers ("combin*," "coadministration," "co-administered," and "regimen") to identify potential combination therapies to enable development of a machine learning algorithm. CONCLUSIONS:Semantic predications from conclusive claims in the biomedical literature can be used to support automated knowledge discovery and knowledge graph construction for combination therapies. A machine learning approach is warranted to take full advantage of the identified markers and other contextual features.

Project description:We explored structural brain connectomes in children with spastic unilateral cerebral palsy (uCP) and its relation to sensory-motor function using graph theory. In 46 children with uCP (mean age = 10 years 7 months ± 2 years 9 months; Manual Ability Classification System I = 15, II = 16, III = 15) we assessed upper limb somatosensory and motor function. We collected multi-shell diffusion-weighted, T1-weighted and T2-FLAIR MRI and identified the corticospinal tract (CST) wiring pattern using transcranial magnetic stimulation. Structural connectomes were constructed using Virtual Brain Grafting-modified FreeSurfer parcellations and multi-shell multi-tissue constrained spherical deconvolution-based anatomically-constrained tractography. Graph metrics (characteristic path length, global/local efficiency and clustering coefficient) of the whole brain, the ipsilesional/contralesional hemisphere, and the full/ipsilesional/contralesional sensory-motor network were compared between lesion types (periventricular white matter (PWM) = 28, cortical and deep gray matter (CDGM) = 18) and CST-wiring patterns (ipsilateral = 14, bilateral = 14, contralateral = 12, unknown = 6) using ANCOVA with age as covariate. Using elastic-net regularized regression we investigated how graph metrics, lesion volume, lesion type, CST-wiring pattern and age predicted sensory-motor function. In both the whole brain and subnetworks, we observed a hyperconnectivity pattern in children with CDGM-lesions compared with PWM-lesions, with higher clustering coefficient (p = [<.001-.047], ηp2 =[0.09-0.27]), characteristic path length (p = .003, ηp2 =0.19) and local efficiency (p = [.001-.02], ηp2 =[0.11-0.21]), and a lower global efficiency with age (p = [.01-.04], ηp2 =[0.09-0.15]). No differences were found between CST-wiring groups. Overall, good predictions of sensory-motor function were obtained with elastic-net regression (R2 = .40-.87). CST-wiring pattern was the strongest predictor for motor function. For somatosensory function, all independent variables contributed equally to the model. In conclusion, we demonstrated the potential of structural connectomics in understanding disease severity and brain development in children with uCP.

Project description:BackgroundUndergraduate biomedical engineering (BME) students interested in pursuing a career in research and development of medical or physiological monitoring devices require a strong foundation in biosignal analysis as well as physiological theory. Applied learning approaches are reported to be effective for reinforcing physiological coursework; therefore, we propose a new laboratory protocol for BME undergraduate physiology courses that integrates both neural engineering and physiological concepts to explore involuntary skeletal muscle reflexes. The protocol consists of two sections: the first focuses on recruiting soleus motor units through transcutaneous electrical nerve stimulation (TENS), while the second focuses on exploring the natural stretch reflex with and without the Jendrassik maneuver. In this case study, third-year biomedical engineering students collected electromyographic (EMG) activity of skeletal muscle contractions in response to peripheral nerve stimulation using a BioRadio Wireless Physiology Monitor system and analyzed the corresponding signal parameters (latency and amplitude) using the MATLAB platform.Results/protocol validationElectrical tibial nerve stimulation successfully recruited M-waves in all 8 student participants and F-waves in three student participants. The students used this data to learn about orthodromic and antidromic motor fiber activation as well as estimate the neural response latency and amplitude. With the stretch reflex, students were able to collect distinct signals corresponding to the tendon strike and motor response. From this, they were able to estimate the sensorimotor conduction velocity. Additionally, a significant increase in the stretch reflex EMG amplitude response was observed when using the Jendrassik maneuver during the knee-jerk response. A student exit survey on the laboratory experience reported that the class found the module engaging and helpful for reinforcing physiological course concepts.ConclusionThis newly developed protocol not only allows BME students to explore physiological responses using natural and electrically-induced involuntary reflexes, but demonstrates that budget-friendly commercially available devices are capable of eliciting and measuring involuntary reflexes in an engaging manner. Despite some limitations caused by the equipment and students' lack of signal processing experience, this new laboratory protocol provides a robust framework for integrating engineering and physiology in an applied approach for BME students to learn about involuntary reflexes, neurophysiology, and neural engineering.

Project description:BACKGROUND:Automatically extracting relations between chemicals and diseases plays an important role in biomedical text mining. Chemical-disease relation (CDR) extraction aims at extracting complex semantic relationships between entities in documents, which contain intrasentence and intersentence relations. Most previous methods did not consider dependency syntactic information across the sentences, which are very valuable for the relations extraction task, in particular, for extracting the intersentence relations accurately. OBJECTIVE:In this paper, we propose a novel end-to-end neural network based on the graph convolutional network (GCN) and multihead attention, which makes use of the dependency syntactic information across the sentences to improve CDR extraction task. METHODS:To improve the performance of intersentence relation extraction, we constructed a document-level dependency graph to capture the dependency syntactic information across sentences. GCN is applied to capture the feature representation of the document-level dependency graph. The multihead attention mechanism is employed to learn the relatively important context features from different semantic subspaces. To enhance the input representation, the deep context representation is used in our model instead of traditional word embedding. RESULTS:We evaluate our method on CDR corpus. The experimental results show that our method achieves an F-measure of 63.5%, which is superior to other state-of-the-art methods. In the intrasentence level, our method achieves a precision, recall, and F-measure of 59.1%, 81.5%, and 68.5%, respectively. In the intersentence level, our method achieves a precision, recall, and F-measure of 47.8%, 52.2%, and 49.9%, respectively. CONCLUSIONS:The GCN model can effectively exploit the across sentence dependency information to improve the performance of intersentence CDR extraction. Both the deep context representation and multihead attention are helpful in the CDR extraction task.

Dataset Information

Exploring Integrative Analysis Using the BioMedical Evidence Graph.

Purpose

Methods

Results

Conclusion

Publications

Exploring Integrative Analysis Using the BioMedical Evidence Graph.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets