昭和20年代, 教室の日常と研究余話(第922回千葉医学会例会・第13回千葉精神科集談会)

<p>Unique MAA Arcs and Mechanistic Genes in Tight Junction Pathway.</p

Prediction of protective immunity by the Dynamic Bayesian Network (DBN).

<p>(<b>A</b>) The Dynamic Bayesian network model representing the learned gene regulatory network structure. Each node represents a continuous variable with a Gaussian distribution. The DBN was trained with the time course data associated with each gene. Relationships between gene nodes, or between the gene node and the PRNT₈₀ node, are represented by arrows as a directed acyclic graph. (<b>B</b>) Example inferencing results on a selected set of gene expression data taken at time window -5, -4, -3 pSN to predict the PRNT₈₀ outcome. Graph indicates strong serologic response and log10(PRNT₈₀) levels sufficient for protection given hypothetical gene expression data. (<b>C</b>) Performance table for model experiment in (B) show high specificity and sensitivity of the model predictions in a time window up taken at –5, -4, -3pSN. Data sets for true negative testing were randomly selected from other genes at the same time points as the true positive gene data sets. Data from five individual animal subjects were employed for the model evaluation.</p

DBGGA GO term analysis on time-shifted data.

<p>(<b>A</b>) Summary table of GO Terms and component gene perturbation by time pre-seroconversion. Only GO terms and their genes with Bayesian score ≥|2.24| are included in analysis. (<b>B-C</b>) Heat maps of perturbed GO terms described by time pre-seroconversion and identified from the Early Phase (time –6, –5, –4, –3 pSN) (<b>B</b>) and the Later Phase (time –2, –1, 0, 1 pSN) (<b>C</b>). Red color indicates activation, green color indicates repression. Intensity of color represents amplitude of perturbation. The list of GO terms shown represent a subset of all perturbed terms that were selected as being most relevant to innate and adaptive immune response.</p

Sliding window correlation (SWC) to identify GO terms associated with serum neutralization titers.

<p>(<b>A</b>) Immunologically important GO terms correlated with log10(PRNT₈₀) listed by time window with associated p-value indicated significance of correlation. (<b>B</b>) Correlated GO terms plotted as log10(PRNT₈₀) vs Normalized GO term DBGGA Bayesian z-scores. The GO term <i>Viral life cycle</i> had a negative correlation with seroconversion at the windowed time points –6, –5, and –4 pSN (upper panel), while <i>Positive regulation of T cell cytokine production</i> shows a positive correlation with seroconversion at the windowed time points –4, –3, and –2 pSN (lower panel).</p

DBGGA pathway analysis on time-shifted data.

<p>(<b>A</b>) Summary table of significantly activated or repressed cellular pathways (Bayesian score ≥|2.24|) on time shifted data. Perturbation of cellular pathways and constituent genes are reported. (<b>B-C</b>) Heat map representation of significantly perturbed pathways at times pre-serum neutralization (pSN). Red color indicates activation, green color indicates repression. Intensity of color represents amplitude of perturbation. Analyses are oriented to the Early Phase (time –6, –5, –4, –3 pSN) (<b>B</b>) or the Late Phase (time –2, –1, 0, 1 pSN) (<b>C</b>) to identify significant pathway perturbations at different periods during the vaccine response.</p

Dynamic Bayesian Gene Group Activation (DBGGA) Pathway analysis.

<p>(<b>A</b>) Summary table of cellular pathways significantly activated or repressed (Bayesian score ≥|2.24|) over the time course of the experiment as determined by the DBGGA tool. (<b>B-C</b>) Read out and heat map of significantly perturbed pathways during days post inoculation (p.i.). Red color indicates activation, green color indicated repression. Intensity of color represents amplitude of perturbation. Analyses are oriented to the Early Phase (days 2–6 p.i.) (<b>B</b>) or the Late Phase (days 7, 10, 14, 21 p.i.) (<b>C</b>) to identify significant perturbations at different periods during the vaccine response.</p

Summary of DBGGA Pathways or GO terms and constituent genes with high correlation to protective antibody response.

<p>(<b>A</b>) A selected set of DBGGA scored pathways or GO terms most correlated with protective antibody response employed for learning the dynamic Bayesian network model for inferencing future protective immune response. (<b>B</b>) A subset of immunologically relevant genes associated with pathways and GO terms listed in (A) that are highly correlative to serologic protection as determined by PRNT₈₀. Various time windows are represented, with time –6, –5, –4 pSN window being the furthest from the designated time of serologic protection.</p

Dynamic Bayesian Gene Group Activation (DBGGA) Gene Ontology (GO) Term analysis.

<p>(<b>A</b>) Summary table of significantly perturbed GO terms and genes described by day post inoculation. Only GO terms and their genes with Bayesian score ≥|2.24| are included in analysis. (<b>B-C</b>) Heat maps of perturbed GO terms described by day post inoculation (p.i.) and identified from the Early Phase (<b>B</b>) and the Later Phase (<b>C</b>). Red color indicates activation, green color indicates repression. Intensity of color represents amplitude of perturbation. The list of GO terms shown represents a subset of all perturbed terms that were selected as being most relevant to innate and adaptive immune response.</p

Serologic and perturbed gene analysis of cattle vaccinated with arMP-12.

<p>(<b>A</b>) Log10 plaque reducing neutralizing titers (Log10(PRNT₈₀)) of test animals prior to and after vaccination with arMP-12. A dilution of 1:80 (log10 = 1.903) was used as the cutoff to determine protection from WT RVFV challenge based on prior published work. (<b>B</b>) Schematic of the immunologic status of test animals by day of experiment: unvaccinated (gray), vaccinated, below PRNT₈₀ cutoff (light red), vaccinated, first day at or above PRNT₈₀ cutoff (dark green), vaccinated, above PRNT₈₀ (light green). (<b>C</b>) Summary count of significantly perturbed genes normalized against unvaccinated samples occurring in at least 50% of animals by day post inoculation, with a |Z-score ≥2.24| and a false discovery rate (FDR) ≤0.05.</p

Sliding Window Correlation of Sets of Genes Associated with Pathways and GO Terms.

<p>Sliding Window Correlation of Sets of Genes Associated with Pathways and GO Terms.</p