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Summary Multi-omic profiling of human peripheral blood is increasingly utilized to identify biomarkers and pathophysiologic mechanisms of disease. The importance of these platforms in clinical and translational studies led us to investigate the impact of delayed blood processing on the numbers and state of peripheral blood mononuclear cells (PBMC) and on the plasma proteome. Similar to previous studies, we show minimal effects of delayed processing on the numbers and general phenotype of PBMC up to 18 hours. In contrast, profound changes in the single-cell transcriptome and composition of the plasma proteome become evident as early as 6 hours after blood draw. These reflect patterns of cellular activation across diverse cell types that lead to progressive distancing of the gene expression state and plasma proteome from native in vivo biology. Differences accumulating during an overnight rest (18 hours) could confound relevant biologic variance related to many underlying disease states., Graphical abstract, Highlights • Studies of human blood cells and plasma are highly sensitive to process variability • Time variability distorts biology in cutting-edge single-cell and multiplex assays • Longitudinal, multi-modal, and aligned data enable data qualification and exploration • Dataset holds potential novel, multi-modal biological correlations and hypotheses, Molecular Physiology ; Immunology ; Proteomics ; Transcriptomics

SUMMARY The majority of supratentorial ependymomas (ST-ependymomas) have few mutations but frequently display chromothripsis of chromosome 11q that generates a fusion between C11orf95 and RELA (RELAFUS). Neural stem cells transduced with RELAFUS ex vivo form ependymomas when implanted in the brain. These tumors display enhanced NF-κB signaling, suggesting that this aberrant signal is the principal mechanism of oncogenesis. However, it is not known whether RELAFUS is sufficient to drive de novo ependymoma tumorigenesis in the brain and, if so, whether these tumors also arise from neural stem cells. We show that RELAFUS drives ST-ependymoma formation from periventricular neural stem cells in mice and that RELAFUS-induced tumorigenesis is likely dependent on a series of cell signaling pathways in addition to NF-κB., Graphical Abstract, In Brief The C11orf95-RELA fusion (RELAFUS) has been found in a distinct subset of supratentorial ependymomas. Ozawa et al. show that RELAFUS is sufficient to drive ST-ependymoma formation from periventricular neural stem cells in mice. Furthermore, they show that RELAFUS-induced tumorigenesis might depend on other cell signaling pathways in addition to NF-κB.

Genetic regulatory networks (GRNs) are complex, large-scale, and spatially and temporally distributed. These characteristics impose challenging demands on software tools for building GRN models, and so there is a need for custom tools. In this paper, we report on our ongoing development of BioTapestry, an open source, freely available computational tool designed specifically for building GRN models. We also outline our future development plans, and give some examples of current applications of BioTapestry.

Original chapter can be found at: http://www.sciencedirect.com/science/book/9780124287655 Copyright Elsevier Ltd. [Full text of this item is not available in the UHRA]