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Maren Depke Results Kidney Gene Expression Pattern in an in vivo Infection Model In the search for specific differences in infection with S. aureus RN1HG ΔsigB vs. infection with RN1HG, the same comparison was performed for the biological replicates separately (for comparison see Fig. R.2.3; and Fig. R.2.4, panel ). This analysis resulted in 7 or 6 sequences/genes which were differentially expressed in the first biological replicate BR1 or the second biological replicate BR2, respectively (Table R.2.1). Both lists did not display any overlap indicating that the few regulated genes were not reproducible in the biological replicates, although statistically significant (Fig. R.2.5 B). Additionally, the statistical significance in the biological replicate BR1 was again caused by one single sample, i. e. by one specific animal, which provided an outlier value to the data set (Fig. R.2.5 C). The same sample accounted for the outlier in the values of the single gene significantly regulated when combining the biological replicates (Fig. R.2.5 A). The statistical significance of the 6 differentially expressed genes in the second biological replicate was not caused by outliers (Fig. R.2.5 D), but the fold change in this comparison was only moderate ranging from to -1.34 to -2.18 (mean: -1.72; median: -1.67). In conclusion, the study could not provide any hints for statistically significant differences in the expression pattern in murine kidney upon infection with S. aureus RN1HG or its isogenic sigB mutant. When asking for the reproducibility of the same treatment in both biological replicates in the light of a possible influence on the detection of differential gene expression between the groups infected with the two different S. aureus strains (for comparison see Fig. R.2.3; and Fig. R.2.4, panel ), 33 sequences (i. e. 26 genes) were significantly different between the replicates of infection with RN1HG, and 62 sequences (i. e. 31 genes) significantly differed between the replicates of infection with RN1HG ΔsigB (Table R.2.1). Of these genes, only a small fraction of approximately 20 % possessed an absolute fold change greater than 2. For these few genes a high expression variation within one biological replicate was observed or the statistical difference even was again due to one outlier array. Additionally, most genes which differed between the replicates did not display any overlap with the genes which were significantly different between the groups infected with the two different S. aureus strains. Only some genes were statistically differentially expressed between the equally treated replicates as well as between infection with RN1HG and RN1HG ΔsigB in the first biological replicate. But as the statistical significance between samples infected with the two strains was only caused by one single outlier value (Fig. R.2.5 C), it was clear that the small difference between biological replicates did not prevent the identification of differential gene expression in the comparison of host reaction to the two infecting S. aureus strains. In summary, the comparison of same treatment groups in different biological replicates revealed minor, negligible differences that did not influence the detection of differential regulation when comparing the groups of infection with different S. aureus strains. The identical reaction to infection with S. aureus RN1HG and S. aureus RN1HG ΔsigB was reliably measured in the array study and the detection of differences was not prevented by biological variation between the two independent infection experiments. 80
Maren Depke BR1 sign DsigB vs wt BR1 sign DsigB vs wt A DsigB Igk-V28 wt infection with RN1HG ΔsigB vs. RN1HG; BR1 and und BR2 BR2 combined DsigB vs wt Igk-V28_DsigB Results Kidney Gene Expression Pattern in an in vivo Infection Model B BR1 sign DsigB vs wt BR1 sign DsigB vs wt 7 0 6 C Igk-V28_DsigB 1 10 100 1000 10000 Igk-V28_wt signal intensity infection with S. aureus RN1HG ΔsigB infection with S. aureus RN1HG wt Igk-V28_wt Cyp11b1_DsigB D sequences/genes differentially expressed between infection with RN1HG ΔsigB and infection with RN1HG in BR1 sequences/genes differentially expressed between infection with RN1HG ΔsigB and infection with RN1HG in BR2 Cyp11b1_DsigB infection BR1 with sign RN1HG DsigB ΔsigB vs wt vs. RN1HG; BR1 Cyp11b1_wt infection with S. aureus RN1HG ΔsigB infection with S. aureus RN1HG wt Igk-V28_DsigB Igk-V28 Cyp11b1_wt Igk-V28_wt 4921521F21Rik_DsigB infectionBR2 withsign RN1HG DsigB ΔsigBvs vs. wt RN1HG; BR2 Cyp11b1_DsigB Cyp11b1 4921521F21Rik_DsigB Cyp11b1_wt 4921521F21Rik_wt Gpr84_DsigB Gpr84 Gpr84_wt 4921521F21Rik_DsigB 4921521F21Rik 4921521F21Rik_wt 4921521F21Rik_wt Star_DsigB Cd274_DsigB Cd274 Cd274_wt Star_DsigB Star Star_wt Star_DsigB Star_wt Cxcl9_DsigB Cxcl9 Cxcl9_wt Hsd3b1_DsigB Cybb_DsigB Hsd3b1 Hsd3b1_wt Star_wt Hsd3b1_DsigB Cybb Cybb_wt Cyp21a1_DsigB Cyp21a1 Cyp21a1_wt Hsd3b1_DsigB Hsd3b1_wt C3ar1_DsigB C3ar1 C3ar1_wt Cyp11a1_DsigB Cyp11a1 Cyp11a1_wt Hsd3b1_wt Cyp21a1_DsigB Plekho2_DsigB Plekho2 Plekho2_wt 1 10 100 1000 10000 signal intensity Cyp21a1_DsigB Fig. R.2.5: Signal intensities Cyp21a1_wt and list comparison for differentially expressed genes. A. Comparison of murine kidney expression profiles after infection with RN1HG ΔsigB and infection with RN1HG with statistical testing results in one differentially expressed gene when combining both available biological replicates. However, the signal intensity is extremely low (not expressed with p > 0.01 on intensity profile level in Rosetta Resolver software) in all arrays except in one array (i. e. a kidney sample) Cyp21a1_wt from one mouse infected with RN1HG (BR1) which is visible as outlier and which causes the statistical significance. Cyp11a1_DsigB B. Comparison of genes differentially regulated between infection with RN1HG and its isogenic sigB mutant in BR1 and BR2. Both 10 biological replicates result 100in completely different 1000 lists of differentially expressed 10000 genes. C, D. Signal intensity values of differentially expressed genes in the comparison of infection with RN1HG ΔsigB and infection with RN1HG in BR1 Cyp11a1_DsigB (C) and in BR2 (D). In BR1, statistical significance is caused by a single array that includes an outlier value. Cyp11a1_wt BR – biological replicate. 10 100 1000 10000 81 1 10 100 1000 10000 signal intensity Cyp11a1_wt1 10 100 1000 10000 1 10 100 1000 10000
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G E N O M E W I D E C H A R A C T E
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Maren Depke C O N T E N T S GENOMEW
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Maren Depke Z U S A M M E N F A S S
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Maren Depke Zusammenfassung der Dis
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Maren Depke S U M M A R Y O F D I S
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Maren Depke Summary of Dissertation
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Maren Depke I N T R O D U C T I O N
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Maren Depke Introduction Besides op
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Maren Depke Introduction Extracellu
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Maren Depke Introduction with heigh
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Maren Depke Introduction 2005). SaP
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Maren Depke Introduction contains a
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Maren Depke Introduction via fibron
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Maren Depke Introduction cathelicid
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Maren Depke Results Host Cell Gene
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Maren Depke Results Pathogen Gene E
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S. aureus RN1HG sample conditions a
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mean normalized intensity mean norm
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mean normalized intensity Maren Dep
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log 2 (ratio) log 2 (ratio) log 2 (
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Maren Depke D I S C U S S I O N A N
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Maren Depke Discussion and Conclusi
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Maren Depke References Athanasopoul
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Maren Depke References Byrne GI, Le
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Maren Depke References Demling R. T
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Maren Depke References Foss GS, Pry
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Maren Depke References Hagopian K,
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Maren Depke References Jin T, Bokar
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Maren Depke References Kwan T, Liu
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Maren Depke References Luster AD, U
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Maren Depke References Namiki S, Na
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Maren Depke References Puccetti P.
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Maren Depke References Siewert E, B
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Maren Depke References van den Akke
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Maren Depke References Yang XL, Sch
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Maren Depke A F F I D A V I T / E R
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Maren Depke Acknowledgments Kidney
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