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Background: The past few years have seen a tremendous increase in the size and complexity of datasets. Scientific and clinical studies must to incorporate datasets that cross multiple spatial and temporal scales to describe a particular phenomenon. The storage and accessibility of these heterogeneous datasets in a way that is useful to researchers and yet extensible to new data types is a major challenge. Methods: In order to overcome these obstacles, we propose the use of data primitives as a common currency between analytical methods. The four data primitives we have identified are time series, text, annotated graph and triangulated mesh, with associated metadata. Using only data primitives to store data and as algorithm input, output, and intermediate results, promotes interoperability, scalability, and reproducibility in scientific studies. Results: Data primitives were used in a multi-omic, multi-scale systems biology study of malaria infection in non-human primates to perform many types of integrative analysis quickly and efficiently. Conclusions: Using data primitives as a common currency for both data storage and for cross talk between analytical methods enables the analysis of complex multi-omic, multi-scale datasets in a reproducible modular fashion., Comment: 10 pages, 3 figures

Characterization of host responses associated with severe malaria through an integrative approach is necessary to understand the dynamics of a \textit{Plasmodium cynomolgi} infection. In this study, we conducted temporal immune profiling, cytokine profiling and transcriptomic analysis of five \textit{Macaca mulatta} infected with \textit{P. cynomolgi}. This experiment resulted in two severe infections, and two mild infections. Our analysis reveals that differential transcriptional up-regulation of genes linked with response to pathogen-associated molecular pattern (PAMP) and pro-inflammatory cytokines is characteristic of hosts experiencing severe malaria. Furthermore, our analysis discovered associations of transcriptional differential regulation unique to severe hosts with specific cellular and cytokine responses. The combined data provide a molecular and cellular basis for the development of severe malaria during \textit{P. cynomolgi} infection., Comment: 10 pages, 8 figures

We derived an ordinary differential equation model to capture the disease dynamics during blood-stage malaria. The model was directly derived from an earlier age-structured partial differential equation model. The original model was simplified due to experimental constraints. Here we calibrated the simplified model with experimental data using a multiple objective genetic algorithm. Through the calibration process, we quantified the removal of healthy red blood cells and the the preferential infection of reticulocytes during \textit{Plamodium cynomolgi} infection of \textit{Macaca mulatta}. The calibration of our model also revealed the existence of host erythropoietic response prior to blood stage infection., Comment: 17 pages, 14 figures

The goals of the Triple Aim of health care and the goals of P4 medicine outline objectives that require a significant health informatics component. However, the goals do not provide specifications about how all of the new individual patient data will be combined in meaningful ways and with data from other sources, like epidemiological data, to promote the health of individuals and society. We seem to have more data than ever before but few resources and means to use it efficiently. We need a general, extensible solution that integrates and homogenizes data of disparate origin, incompatible formats, and multiple spatial and temporal scales. To address this problem, we introduce the Scientific Knowledge Extraction from Data (SKED) architecture, as a technology-agnostic framework to minimize the overhead of data integration, permit reuse of analytical pipelines, and guarantee reproducible quantitative results. The SKED architecture consists of a Resource Allocation Service to locate resources, and the definition of data primitives to simplify and harmonize data. SKED allows automated knowledge discovery and provides a platform for the realization of the major goals of modern health care., Comment: 8 pages, 4 figures

Quantification of system-wide perturbations from time series -omic data (i.e. a large number of variables with multiple measures in time) provides the basis for many downstream hypothesis generating tools. Here we propose a method, Massively Parallel Analysis of Time Series (MPATS) that can be applied to quantify transcriptome-wide perturbations. The proposed method characterizes each individual time series through its $\ell_1$ distance to every other time series. Application of MPATS to compare biological conditions produces a ranked list of time series based on their magnitude of differences in their $\ell_1$ representation, which then can be further interpreted through enrichment analysis. The performance of MPATS was validated through its application to a study of IFN$\alpha$ dendritic cell responses to viral and bacterial infection. In conjunction with Gene Set Enrichment Analysis (GSEA), MPATS produced consistently identified signature gene sets of anti-bacterial and anti-viral response. Traditional methods such as EDGE and GSEA Time Series (GSEA-TS) failed to identify the relevant signature gene sets. Furthermore, the results of MPATS highlighted the crucial functional difference between STAT1/STAT2 during anti-viral and anti-bacterial response. In our simulation study, MPATS exhibited acceptable performance with small group size (n = 3), when the appropriate effect size is considered. This method can be easily adopted for other -omic data types., Comment: 18 pages, 8 figures