By combining various cancer cell line (CCL) drug screening panels, the size of the data has grown significantly to begin understanding how advances in deep learning can advance drug response predictions. In this paper we train >35,000 neural network models, sweeping over common featurization techniques. We found the RNA-seq to be highly redundant and informative even with subsets larger than 128 features. We found the inclusion of single nucleotide polymorphisms (SNPs) coded as count matrices improved model performance significantly, and no substantial difference in model performance with respect to molecular featurization between the common open source MOrdred descriptors and Dragon7 descriptors. Alongside this analysis, we outline data integration between CCL screening datasets and present evidence that new metrics and imbalanced data techniques, as well as advances in data standardization, need to be developed.
The recent advances in single-cell technologies have enabled us to profile genomic features at unprecedented resolution and datasets from multiple domains are available, including datasets that profile different types of genomic features and datasets that profile the same type of genomic features across different species. These datasets typically have different powers in identifying the unknown cell types through clustering, and data integration can potentially lead to a better performance of clustering algorithms. In this work, we formulate the problem in an unsupervised transfer learning framework, which utilizes knowledge learned from auxiliary dataset to improve the clustering performance of target dataset. The degree of shared information among the target and auxiliary datasets can vary, and their distributions can also be different. To address these challenges, we propose an elastic coupled co-clustering based transfer learning algorithm, by elastically propagating clustering knowledge obtained from the auxiliary dataset to the target dataset. Implementation on single-cell genomic datasets shows that our algorithm greatly improves clustering performance over the traditional learning algorithms. The source code and data sets are available at https://github.com/cuhklinlab/elasticC3.
Drug repositioning offers an effective solution to drug discovery, saving both time and resources by finding new indications for existing drugs. Typically, a drug takes effect via its protein targets in the cell. As a result, it is necessary for drug development studies to conduct an investigation into the interrelationships of drugs, protein targets, and diseases. Although previous studies have made a strong case for the effectiveness of integrative network-based methods for predicting these interrelationships, little progress has been achieved in this regard within drug repositioning research. Moreover, the interactions of new drugs and targets (lacking any known targets and drugs, respectively) cannot be accurately predicted by most established methods. In this paper, we propose a novel semi-supervised heterogeneous label propagation algorithm named Heter-LP, which applies both local as well as global network features for data integration. To predict drug-target, disease-target, and drug-disease associations, we use information about drugs, diseases, and targets as collected from multiple sources at different levels. Our algorithm integrates these various types of data into a heterogeneous network and implements a label propagation algorithm to find new interactions. Statistical analyses of 10-fold cross-validation results and experimental analysis support the effectiveness of the proposed algorithm.
Motivation: Biological data and knowledge bases increasingly rely on Semantic Web technologies and the use of knowledge graphs for data integration, retrieval and federated queries. In the past years, feature learning methods that are applicable to graph-structured data are becoming available, but have not yet widely been applied and evaluated on structured biological knowledge. Results: We develop a novel method for feature learning on biological knowledge graphs. Our method combines symbolic methods, in particular knowledge representation using symbolic logic and automated reasoning, with neural networks to generate embeddings of nodes that encode for related information within knowledge graphs. Through the use of symbolic logic, these embeddings contain both explicit and implicit information. We apply these embeddings to the prediction of edges in the knowledge graph representing problems of function prediction, finding candidate genes of diseases, protein-protein interactions, or drug target relations, and demonstrate performance that matches and sometimes outperforms traditional approaches based on manually crafted features. Our method can be applied to any biological knowledge graph, and will thereby open up the increasing amount of Semantic Web based knowledge bases in biology to use in machine learning and data analytics. Availability and Implementation: https://github.com/bio-ontology-research-group/walking-rdf-and-owl Contact: [email omitted]
We introduce a novel Bayesian hybrid matrix factorisation model (HMF) for data integration, based on combining multiple matrix factorisation methods, that can be used for in- and out-of-matrix prediction of missing values. The model is very general and can be used to integrate many datasets across different entity types, including repeated experiments, similarity matrices, and very sparse datasets. We apply our method on two biological applications, and extensively compare it to state-of-the-art machine learning and matrix factorisation models. For in-matrix predictions on drug sensitivity datasets we obtain consistently better performances than existing methods. This is especially the case when we increase the sparsity of the datasets. Furthermore, we perform out-of-matrix predictions on methylation and gene expression datasets, and obtain the best results on two of the three datasets, especially when the predictivity of datasets is high.
Relational data sources are still one of the most popular ways to store enterprise or Web data, however, the issue with relational schema is the lack of a well-defined semantic description. A common ontology provides a way to represent the meaning of a relational schema and can facilitate the integration of heterogeneous data sources within a domain. Semantic labeling is achieved by mapping attributes from the data sources to the classes and properties in the ontology. We formulate this problem as a multi-class classification problem where previously labeled data sources are used to learn rules for labeling new data sources. The majority of existing approaches for semantic labeling have focused on data integration challenges such as naming conflicts and semantic heterogeneity. In addition, machine learning approaches typically have issues around class imbalance, lack of labeled instances and relative importance of attributes. To address these issues, we develop a new machine learning model with engineered features as well as two deep learning models which do not require extensive feature engineering. We evaluate our new approaches with the state-of-the-art.
The rapid development of high-throughput technologies has enabled the generation of data from biological or disease processes that span multiple layers, like genomic, proteomic or metabolomic data, and further pertain to multiple sources, like disease subtypes or experimental conditions. In this work, we propose a general statistical framework based on Gaussian graphical models for horizontal (i.e. across conditions or subtypes) and vertical (i.e. across different layers containing data on molecular compartments) integration of information in such datasets. We start with decomposing the multi-layer problem into a series of two-layer problems. For each two-layer problem, we model the outcomes at a node in the lower layer as dependent on those of other nodes in that layer, as well as all nodes in the upper layer. We use a combination of neighborhood selection and group-penalized regression to obtain sparse estimates of all model parameters. Following this, we develop a debiasing technique and asymptotic distributions of inter-layer directed edge weights that utilize already computed neighborhood selection coefficients for nodes in the upper layer. Subsequently, we establish global and simultaneous testing procedures for these edge weights. Performance of the proposed methodology is evaluated on synthetic and real data.