Top 24 Over-expressed and 34 Under-expressed Genes in MRSA AHO.

<p>Genes associated to SIS in bold.</p

Module Analysis of Gene Expression Profile in Whole Blood From Patients with MRSA AHO.

<p>Gene expression in one of the subjects within the healthy control group revealed an unusual array of cellular expression. This subject was excluded and microarray statistical analysis was repeated without his information. Gene expression levels were compared between healthy controls and patients with MRSA AHO on a module by module analysis. Each column represents a subject and each row a cell type. Colored spots represent the percentage of significant over-expressed (red) or under expressed (blue) transcripts (Mann-Whitney p<0.05). The intensity of the color refers to the number of transcripts within each of the pre-selected modules not the actual fold change that is up or down regulated compared to healthy controls. Modular analysis identified that patients had upregulation of innate immunity and mild downregulation of adaptive immunity.</p

Severity of Illness Score (SIS) Calculation for Children Hospitalized with MRSA AHO During Study Time Period.

<p>Severity of Illness Score (SIS) Calculation for Children Hospitalized with MRSA AHO During Study Time Period.</p

Module Analysis of Gene List Applied To an Independent Set of Patients Revealed The Same Modular Map.

<p>Average modular transcriptional fingerprint of patients with MRSA AHO showed that patients had upregulation of innate immunity including platelet, neutrophil and erythroid-related genes. Analysis also showed that patients had mild downregulation of adaptive immunity including B- cell, T-cell and NK cell-related genes. Interferon signature was not noted in this analysis.</p

Correlation of Gene Over and Under-Expression and Severity of Illness Score (SIS).

<p>Statistical correlation (Pearson, Spearman, Pearson Log Gene and Pearson Log-Log) of severity of illness score and quantitative gene expression was significant for five genes. <b>A)</b> RETN (resistin gene), SORT 1 (sortilin 1 gene) and P2RX1 (purinergic receptor P2X, ligand-gated ion channel 1) showed over-expression. <b>B)</b> LOC641788 (similar to CDC26 subunit of anaphase promoting complex) and STAT 4 (signal transducer and activator of transcription 4) showed under-expression. Of those genes, RETN and STAT 4 had the strongest correlation coefficients (RETN: R2 = 0.8 and STAT 4: R2 = –0.83).</p

Gene Expression Biosignature in Whole Blood From Healthy Controls and Patients With MRSA AHO.

<p>Complete statistical analysis (Welch t-Test with Benjamini - Hochberg false discovery rate, p<0.05) between the two groups (healthy control group with 9 subjects and MRSA AHO group with 10 subjects) identified 58 genes (24 over-expressed and 34 under-expressed) which significantly differentiated children with MRSA AHO from the healthy controls.</p

Clinical Characteristics of Children Hospitalized with MRSA AHO During Study Time Period.

<p>Subjects excluded from statistical analysis in bold.</p

Gene Expression Biosignature in Whole Blood From Healthy Controls and Patients With MRSA AHO.

<p>Statistical tests were used to compare the two study groups (Welch’s t-test, p<0.05 with Benjamini-Hochberg’s method). <b>A)</b> Analysis of the healthy control group with 9 subjects and the MRSA AHO group with 10 patients yielded 23,023 genes expressed at statistically different levels. Hierarchical clustering, used to organize those genes to reveal differential expression, supports that patients with MRSA AHO have unique signatures that classify them as different from controls. <b>B)</b> Further statistical analysis between the healthy controls and the MRSA AHO group yielded 269 genes expressed at different levels.</p

Clinical and Laboratory Features Determining Severity of Illness Score of Children with Acute Hematogenous Osteomyelitis.

<p>Male (M); Female (F); C-reactive protein (CRP) initial, 48 hours and 96 hours (mg/dL); Respiratory rate (RR%) – percentage of the mid-range norm breaths per minute for age; Antibiotics (abx); Yes (Y); No (N); Intensive Care Unit (ICU) admission (Adm); Disseminated disease (Dissem Dis) includes: multi-focal infection, pneumonia, septic pulmonary embolism, deep venous thrombosis, septic shock, meningitis, or endocarditis.</p><p>Clinical and Laboratory Features Determining Severity of Illness Score of Children with Acute Hematogenous Osteomyelitis.</p

Dendrogram of the differences between study isolates (EA1 through EA12) and the USA 300 reference strain at the gamma hemolysin subunit (HlgA) (left) and dendrogram of the polymorphisms of the gamma hemolysin subunit of the study isolates (right).

<p>The tree was generated by neighbor joining analysis with a bootstrap of 10,000. The numbers refer to the confidence of related associations. Higher numbers indicate greater confidence.</p