Identifying biologically relevant genes via multiple heterogeneous data sources

Graph model are increasingly popular among modern applications for its ability to model complex relationships between entities. Users tend to query the data as a graph with graph operations (e.g., graph navigation and exploration). However, a large fraction of the data resides in relational databases or other storage systems. Challenges arise in uniformly querying multiple heterogeneous data sources as a graph. Traditional solutions are limited by time-consuming data integration, expensive development effort, and incomplete query requirements. Thus, we developed Lynx, a general graph query framework, to simplify querying graph data by converting complex statements into basic graph operations. Instead of connecting directly to the data sources, Lynx retrieves data through user-implemented interfaces for those graph operations. We demonstrate Lynx's capabilities through real-world scenarios, showcasing Lynx's ability to process graph queries on multiple heterogeneous data sources and also to be used as a generic graph query engine development framework.

Entity alignment is the problem of identifying which entities in a data source refer to the same real-world entity in the others. Identifying entities across heterogeneous data sources is paramount to many research fields, such as data cleaning, data integration, information retrieval and machine learning. The aligning process is not only overwhelmingly expensive for large data sources since it involves all tuples from two or more data sources, but also need to handle heterogeneous entity attributes. In this paper, we propose an unsupervised approach, called EnAli, to match entities across two or more heterogeneous data sources. EnAli employs a generative probabilistic model to incorporate the heterogeneous entity attributes via employing exponential family, handle missing values, and also utilize the locality sensitive hashing schema to reduce the candidate tuples and speed up the aligning process. EnAli is highly accurate and efficient even without any ground-truth tuples. We illustrate the performance of EnAli on re-identifying entities from the same data source, as well as aligning entities across three real data sources. Our experimental results manifest that our proposed approach outperforms the comparable baseline.

Personalized treatments and targeted therapies are the most promising approaches to treat complex diseases, especially for cancer. However, drug resistance is often acquired after treatments. To overcome or reduce drug resistance, treatments using drug combinations have been actively investigated in the literature. Existing methods mainly focus on chemical properties of drugs for potential combination therapies without considering relationships among different diseases. Also, they often do not consider the rich knowledge of drugs and diseases, which can enhance the prediction of drug combinations. This motivates us to develop a new computational method that can predict the beneficial drug combinations. We propose DrugCom, a tensor-based framework for computing drug combinations across different diseases by integrating multiple heterogeneous data sources of drugs and diseases. DrugCom first constructs a primary third-order tensor (i.e., drug×drug ×disease) and several similarity matrices from multiple data sources regarding drugs (e.g., chemical structure) and diseases (e.g., disease phenotype). DrugCom then formulates an objective function, which simultaneously factorizes coupled tensor and matrices to reveal the molecular mechanisms of drug synergy. We adopt the alternating direction method of multipliers algorithm to effectively solve the optimization problem. Extensive experimental studies using real-world datasets demonstrate superior performance of DrugCom.

In recent years, huge different biological databases have been stored in various locations. Using distinct data sets from multiple sources results in more reliable data analysis. However, it is so difficult to combine heterogeneous data in one single server. The most obvious reasons include data privacy, large data sizes, costs, and different geographical locations of data sources. In this paper, we present two new algorithms for clustering data from multiple remote data sources using kernel k-means. The first algorithm is the center-based algorithm built on k-means algorithm. The second algorithm uses distributed kernel k-means over multiple data sources. In the distributed scheme, clustering methods are executed only on their local data sources themselves. Partial clustering results are synched between data sources. To evaluate performance of our proposed algorithms, we merged all data from different sources into one large data set to perform kernel k-means. The results showed that our center-based algorithm greatly reduced transmission data between data sources while still yielding acceptable clustering results. Our distributed kernel k-means algorithm achieved even better performance. The clustering results are very close to those generated by kernel k-means on one merged data set.

BackgroundProtein-protein interaction (PPI) prediction remains a central task in systems biology to achieve a better and holistic understanding of cellular and intracellular processes. Recently, an increasing number of computational methods have shifted from pair-wise prediction to network level prediction. Many of the existing network level methods predict PPIs under the assumption that the training network should be connected. However, this assumption greatly affects the prediction power and limits the application area because the current golden standard PPI networks are usually very sparse and disconnected. Therefore, how to effectively predict PPIs based on a training network that is sparse and disconnected remains a challenge.ResultsIn this work, we developed a novel PPI prediction method based on deep learning neural network and regularized Laplacian kernel. We use a neural network with an autoencoder-like architecture to implicitly simulate the evolutionary processes of a PPI network. Neurons of the output layer correspond to proteins and are labeled with values (1 for interaction and 0 for otherwise) from the adjacency matrix of a sparse disconnected training PPI network. Unlike autoencoder, neurons at the input layer are given all zero input, reflecting an assumption of no a priori knowledge about PPIs, and hidden layers of smaller sizes mimic ancient interactome at different times during evolution. After the training step, an evolved PPI network whose rows are outputs of the neural network can be obtained. We then predict PPIs by applying the regularized Laplacian kernel to the transition matrix that is built upon the evolved PPI network. The results from cross-validation experiments show that the PPI prediction accuracies for yeast data and human data measured as AUC are increased by up to 8.4 and 14.9% respectively, as compared to the baseline. Moreover, the evolved PPI network can also help us leverage complementary information from the disconnected training network and multiple heterogeneous data sources. Tested by the yeast data with six heterogeneous feature kernels, the results show our method can further improve the prediction performance by up to 2%, which is very close to an upper bound that is obtained by an Approximate Bayesian Computation based sampling method.ConclusionsThe proposed evolution deep neural network, coupled with regularized Laplacian kernel, is an effective tool in completing sparse and disconnected PPI networks and in facilitating integration of heterogeneous data sources.

Detecting functional modules from protein-protein interaction (PPI) networks is an active research area with many practical applications. However, there is always a critical concern on the false PPI interactions which are derived from the high-throughput experiments and the unsatisfactory results obtained from single PPI network with severe information insufficiency. To address this problem, we propose a Collective Non-negative Matrix Factorization (CoNMF) based soft clustering method which efficiently integrates information of gene ontology (GO), gene expression data and PPI networks. In our method, the three data sources are formed into two graphs with similarity adjacency matrices and these graphs are approximated by a matrix factorization with their common factor which provides the straight-forward interpretation of clustering results. Extensive experiments show that we can improve the module detection performance by integrating multiple biological data sources and that CoNMF yields superior results compared to other multiple data sources fusion methods by identifying a larger number of more precise protein modules with actual biological meaning and certain degree of overlapping.

ObjectiveBiomedical research increasingly relies on the integration of information from multiple heterogeneous data sources. Despite the fact that structural and terminological aspects of interoperability are interdependent and rely on a common set of requirements, current efforts typically address them in isolation. We propose a unified ontology-based knowledge framework to facilitate interoperability between heterogeneous sources, and investigate if using the LexEVS terminology server is a viable implementation method.Materials and methodsWe developed a framework based on an ontology, the general information model (GIM), to unify structural models and terminologies, together with relevant mapping sets. This allowed a uniform access to these resources within LexEVS to facilitate interoperability by various components and data sources from implementing architectures.ResultsOur unified framework has been tested in the context of the EU Framework Program 7 TRANSFoRm project, where it was used to achieve data integration in a retrospective diabetes cohort study. The GIM was successfully instantiated in TRANSFoRm as the clinical data integration model, and necessary mappings were created to support effective information retrieval for software tools in the project.ConclusionsWe present a novel, unifying approach to address interoperability challenges in heterogeneous data sources, by representing structural and semantic models in one framework. Systems using this architecture can rely solely on the GIM that abstracts over both the structure and coding. Information models, terminologies and mappings are all stored in LexEVS and can be accessed in a uniform manner (implementing the HL7 CTS2 service functional model). The system is flexible and should reduce the effort needed from data sources personnel for implementing and managing the integration.

Combining in-car multiple sensors measuring parameters that can be used to improve both safety and efficiency with a plethora of external data sources (e.g., traffic conditions, weather) which, if properly used, can significantly improve the overall trip experience. One source that can help the navigation and provide "context awareness", especially for autonomous driving, are the High Definition (HD) maps, which have recently witnessed a tremendous growth of popularity in vehicular technology and use. As they are limited to a particular geographic area with respect to a given point along a trip, different portions need to be downloaded (and processed) on multiple occasions throughout a given trip, along with the other data from internal and external sources. We take a first step towards formalizing the problem of Predicting Map Data Consumption (PMDC) in the future time instants for a given trip, based on a (time) window from its history, and investigate the use of Long Short-Term Memory (LSTM) networks - a special type of Recurrent Neural Networks (RNN). Significant efforts were focused on generating an appropriate dataset for this study, towards which we fused the information available in multiple heterogeneous data sources. We conducted experimental observations demonstrating the benefits of the proposed approach.

ABSTRACT
 ObjectivesThe objective was to deliver a platform to accelerate collaborative research into the genetics of dementia. The project is part of a larger effort to establish a platform for research incorporating components related to epidemiological data, imaging, wearable technology and tissue banking with initiatives to link these different data sets.
 The genomics platform aimed to address a number of challenges encountered by researchers:
 
 Enabling patient-level linkage between genomic and other datasets
 Selection of study cohorts using genotypic and phenotypic characteristics
 Collaborating with other groups to perform large-scale meta analysis
 Supporting repeatable analysis workflows
 
 ApproachThe genomics platform was developed using a mixture of open source, commercial and bespoke components developed for this project. It is designed to securely handle data and scale to cope with increasing data volumes as well as the quantity and complexity of research undertaken.
 It is located in a data centre where researchers can access, explore and analyse the data in a secure environment addressing data security and privacy concerns.
 The platform integrates with a supercomputer allowing complex analysis of data to be undertaken easily using novel code or predefined workflows.
 The platform was designed and developed through close collaboration with a prominent academic research team.
 ResultsWe have created a collaborative genomics informatics platform that provides efficient and intuitive selection of study cohorts from multiple data sources, with potentially varying data formats and types, based on both genotypic and phenotypic characteristics. Researchers can combine cohorts definitions using set operations and publish these definitions allowing other researchers to apply them to other datasets.
 There is an internet accessible portal which allows researchers to share results of their analysis and support meta analysis of this research. A sophisticated search engine allows these results to be found based on genetic information or annotations. This portal accelerates meta-analysis, an intrinsically collaborative endeavour in genomics research.
 There is also close integration with HPC (High Performance Computing) resources for computationally expensive tasks. The platform is underpinned by analytical workflows that not only accelerate and enable reproducible research, but reduce the technical barriers to its use.
 The platform enables patient-level linkage with other non-genomics data sources through integration with other research platforms.
 ConclusionThe developed genomics informatics platform provides a step-change in this type of genetic research, accelerating reproducible collaborative research across multiple disparate organisations and data sources, of varying type and complexity.

Future Trends in CT for Coronary Artery Disease: From Diagnosis to Prevention.

It is challenging to identify meaningful gene networks because biological interactions are often condition-specific and confounded with external factors. It is necessary to integrate multiple sources of genomic data to facilitate network inference. For example, one can jointly model expression datasets measured from multiple tissues with molecular marker data in so-called genetical genomic studies. In this paper, we propose a joint conditional Gaussian graphical model (JCGGM) that aims for modeling biological processes based on multiple sources of data. This approach is able to integrate multiple sources of information by adopting conditional models combined with joint sparsity regularization. We apply our approach to a real dataset measuring gene expression in four tissues (kidney, liver, heart, and fat) from recombinant inbred rats. Our approach reveals that the liver tissue has the highest level of tissue-specific gene regulations among genes involved in insulin responsive facilitative sugar transporter mediated glucose transport pathway, followed by heart and fat tissues, and this finding can only be attained from our JCGGM approach.

Understanding the functional mechanisms of the complex biological system as a whole is drawing more and more attention in global health care management. Traditional Chinese Medicine (TCM), essentially different from Western Medicine (WM), is gaining increasing attention due to its emphasis on individual wellness and natural herbal medicine, which satisfies the goal of integrative medicine. However, with the explosive growth of biomedical data on the Web, biomedical researchers are now confronted with the problem of large-scale data analysis and data query. Besides that, biomedical data also has a wide coverage which usually comes from multiple heterogeneous data sources and has different taxonomies, making it hard to integrate and query the big biomedical data. Embedded with domain knowledge from different disciplines all regarding human biological systems, the heterogeneous data repositories are implicitly connected by human expert knowledge. Traditional search engines cannot provide accurate and comprehensive search results for the semantically associated knowledge since they only support keywords-based searches. In this paper, we present BioTCM-SE, a semantic search engine for the information retrieval of modern biology and TCM, which provides biologists with a comprehensive and accurate associated knowledge query platform to greatly facilitate the implicit knowledge discovery between WM and TCM.

Mashups are new Web 2.0 applications that seamlessly combine contents from multiple heterogeneous data sources into one integrated browser environment. The hallmark of these applications is to facilitate dynamic information sharing and analysis, thereby creating a more integrated and convenient experience for end-users. As mashups evolve into portals designed to offer convenient access to information on critical domains, such as banking, shopping, investment, enterprise mashups, and Web desktops, concerns to protect clients' personal information and trade secrets become important, thereby motivating the need for strong security guarantees. We develop a security architecture that provides high assurance on the mutual authentication, data confidentiality, and message integrity of mashup applications. In this paper, we describe the design and implementation of OpenMashupOS (OMOS), an open-source browser independent framework for secure inter-domain communication and mashup development.

Data integration is a crucial step in cancer related bioinformatics studies. Bayesian Networks (BNs) is one of the most commonly used methods for integration of multiple data sources. In this paper, we present a modified BN model that can capture and integrate heterogeneous data to increase its predictive performance. The model allows us to infer aberrant networks with scale-free and small world properties, and to group molecules into functional modules or pathways based on the primary function and biological features. Application of this method to gene and protein biomarkers of hepatocelluar carcinoma (HCC) led to identification of modules that significantly contribute to HCC development and progression. The modules include cell cycle dysregulation, increased angiogenesis (e.g., vascular endothelial growth factor, blood vessel morphogenesis), oxidative metabolic alterations, and aberrant activation of signaling pathways involved in cellular proliferation, survival and differentiation (e.g., Wnt pathways). The central findings and conclusions derived from our modified BN model are consistent with those previously reported results.

In this paper, we focus on the visualization of heterogeneous semantic networks obtained from multiple data sources. A semantic network comprising a set of entities and relationships is often used for representing knowledge derived from textual data or database records. Although the semantic networks created for the same domain at different data sources may cover a similar set of entities, these networks could also be very different because of naming conventions, coverage, view points, and other reasons. Since digital libraries often contain data from multiple sources, we propose a visualization tool to integrate and analyze the differences among multiple social networks. Through a case study on two terrorism-related semantic networks derived from Wikipedia and Terrorism Knowledge Base (TKB) respectively, the effectiveness of our proposed visualization tool is demonstrated.