MOTIVATION: Transcriptomics is a common approach to identify changes in gene expression induced by a disease state. Standard transcriptomic analyses consider differentially expressed genes (DEGs) as indicative of disease states so only a few genes would be treated as signals when the effect size is small, such as in brain tissue. For tissue with small effect sizes, if the DEGs do not belong to a pathway known to be involved in the disease, there would be little left in the transcriptome for researchers to follow up with. RESULTS: We developed RNA Solutions: Synthesizing Information to Support Transcriptomics (RNASSIST), a new approach to identify hidden signals in transcriptomic data by linking differential expression and co-expression networks using machine learning. We applied our approach to RNA-seq data of post-mortem brains that compared the Alcohol Use Disorder (AUD) group with the control group. Many of the candidate genes are not differentially expressed so would likely be ignored by standard transcriptomic analysis pipelines. Through multiple validation strategies, we concluded that these RNASSIST-identified genes likely play a significant role in AUD. AVAILABILITY AND IMPLEMENTATION: The RNASSIST algorithm is available at https://github.com/netrias/rnassist and both the software and the data used in RNASSIST are available at https://figshare.com/articles/software/RNAssist_Software_and_Data/16617250. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

MOTIVATION: Applications in synthetic and systems biology can benefit from measuring whole-cell response to biochemical perturbations. Execution of experiments to cover all possible combinations of perturbations is infeasible. In this paper, we present the host response model (HRM), a machine learning approach that maps response of single perturbations to transcriptional response of the combination of perturbations. RESULTS: The HRM combines high-throughput sequencing with machine learning to infer links between experimental context, prior knowledge of cell regulatory networks, and RNASeq data to predict a gene's dysregulation. We find that the HRM can predict the directionality of dysregulation to a combination of inducers with an accuracy of >90% using data from single inducers. We further find that the use of prior, known cell regulatory networks doubles the predictive performance of the HRM (an R2 from 0.3 to 0.65). The model was validated in two organisms, Escherichia coli and Bacillus subtilis, using new experiments conducted after training. Finally, while the HRM is trained with gene expression data, the direct prediction of differential expression makes it possible to also conduct enrichment analyses using its predictions. We show that the HRM can accurately classify >95% of the pathway regulations. The HRM reduces the number of RNASeq experiments needed as responses can be tested in silico prior to the experiment. AVAILABILITY AND IMPLEMENTATION: The HRM software and tutorial are available at https://github.com/sd2e/CDM and the configurable differential expression analysis tools and tutorials are available at https://github.com/SD2E/omics_tools. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Graph analysis can capture relationships between network entities and can be used to identify and rank anomalous hosts, users, or applications from various types of cyber logs. It is often the case that the data in the logs can be represented as a bipartite graph (e.g. internal IP-external IP, user-application, or client-server). State-of-the-art graph based anomaly detection often generalizes across all types of graphs - namely bipartite and non-bipartite. This confounds the interpretation and use of specific graph features such as degree, page rank, and eigencentrality that can provide a security analyst with situational awareness and even insights to potential attacks on enterprise scale networks. Furthermore, graph algorithms applied to data collected from large, distributed enterprise scale networks require accompanying methods that allow them to scale to the data collected. In this paper, we provide a novel, scalable, directional graph projection framework that operates on cyber logs that can be represented as bipartite graphs. We also present methodologies to further narrow returned results to anomalous/outlier cases that may be indicative of a cyber security event. This framework computes directional graph projections and identifies a set of interpretable graph features that describe anomalies within each partite.

Data from cyber logs can often be represented as a bipartite graph (e.g. internal IP-external IP, user-application, or client-server). State-of-the-art graph based anomaly detection often generalizes across all types of graphs - namely bipartite and non-bipartite. This confounds the interpretation and use of specific graph features such as degree, page rank, and eigencentrality that can provide a security analyst with rapid situational awareness of their network. Furthermore, graph algorithms applied to data collected from large, distributed enterprise scale networks require accompanying methods that allow them to scale to the data collected. In this paper, we provide a novel, scalable, directional graph projection framework that operates on cyber logs that can be represented as bipartite graphs. This framework computes directional graph projections and identifies a set of interpretable graph features that describe anomalies within each partite.

BACKGROUND: Computer-based pathway discovery is concerned with two important objectives: pathway identification and analysis. Conventional mining and modeling approaches aimed at pathway discovery are often effective at achieving either objective, but not both. Such limitations can be effectively tackled leveraging a Web service-based modeling and mining approach. RESULTS: Inspired by molecular recognitions and drug discovery processes, we developed a Web service mining tool, named PathExplorer, to discover potentially interesting biological pathways linking service models of biological processes. The tool uses an innovative approach to identify useful pathways based on graph-based hints and service-based simulation verifying user's hypotheses. CONCLUSION: Web service modeling of biological processes allows the easy access and invocation of these processes on the Web. Web service mining techniques described in this paper enable the discovery of biological pathways linking these process service models. Algorithms presented in this paper for automatically highlighting interesting subgraph within an identified pathway network enable the user to formulate hypothesis, which can be tested out using our simulation algorithm that are also described in this paper.

The Web is transforming from a Web of data to a Web of both Semantic data and services. This trend is providing us with increasing opportunities to compose potentially interesting and useful services from existing services. While we may not sometimes have the specific queries needed in top-down service composition approaches to identify them, the early and proactive exposure of these opportunities will be key to harvest the great potential of the large body of Web services. In this paper, we propose a Web service mining framework that allows unexpected and interesting service compositions to automatically emerge in a bottom-up fashion. We present several mining techniques aiming at the discovery of such service compositions. We also present evaluation measures of their interestingness and usefulness. As a novel application of this framework, we demonstrate its effectiveness and potential by applying it to service-oriented models of biological processes for the discovery of interesting and useful pathways.

We propose a service mining framework for exploring interesting compositions of existing Web services. The framework first screens Web services for composition leads using a "coarse-grained" filtering approach. It then verifies these leads based on runtime conditions. Top candidates are selected from the verified leads and evaluated for their interestingness. We present algorithms to automate the screening phase of the framework. Finally, we study the effects of key variables on lead compositions' interestingness. As a motivating example, we apply these algorithms to the field of biological pathway discovery and rely on knowledge obtained from reverse engineering online resources to assess their effectiveness.