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. 2018 Apr 26;9:874. doi: 10.3389/fimmu.2018.00874

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Copyright © 2018 Mayeux, Escalante, Christy, Pawar, Kono and Pollard.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Correlations of biomarkers in silica-exposed diversity outbred mice. (A) Correlation matrix of Spearman’s correlation coefficient (r_s) values for mice exposed transorally to 5 or 10 mg of crystalline silica. Spearman’s r_s values were calculated using pairwise deletion and represented by a color gradient scale with red = 1, yellow = 0, and green = −1. (B) Hierarchical cluster analysis of phenotypes and samples using a complete linkage clustering method and Spearman Rank Correlation as the similarity metric. Values are reported as relative change from the average of all samples for each phenotype with red = positive relative change, black = no difference, green = negative relative change, and gray = no data available. Dose groups are indicated by the color bar below the sample cluster with blue = 0 mg, purple = 5 mg, and yellow = 10 mg. Separate clusters are defined by a, b, c, and d. Abbreviations: TLS, total lung score; Peri, perivasculitis and peribronchitis; Alv, alveolitis; BALF cell, bronchial alveolar lavage fluid (BALF) total cell number; BALF Prot, BALF protein levels; LDH, lactate dehydrogenase (LDH) activity; SPW, spleen weight; ANA12, anti-nuclear antibody (ANA) score after 12 weeks of exposure; ENA5, designed for the detection of anti-Sm, -RNP, -SS-A (60 kDa and 52 kDa), -SS-B, and -Scl-70 IgG antibodies; RNP, anti-RNP IgG; Sm, anti-Sm IgG; SSA, anti-SSA IgG; SSB, anti-SSB IgG; dsDNA, anti-dsDNA IgG; Chrom, anti-chromatin IgG, ANA4, ANA score after 4 weeks of exposure; ANA8, ANA score after 8 weeks of exposure; ANAPre, ANA score before exposure; BW, body weight; GN, glomerulonephritis; ProtStrip, urine protein using ChemStrip assay.

Correlations of biomarkers in silica-exposed diversity outbred mice. (A) Correlation matrix of Spearman’s correlation coefficient (r_s) values for mice exposed transorally to 5 or 10 mg of crystalline silica. Spearman’s r_s values were calculated using pairwise deletion and represented by a color gradient scale with red = 1, yellow = 0, and green = −1. (B) Hierarchical cluster analysis of phenotypes and samples using a complete linkage clustering method and Spearman Rank Correlation as the similarity metric. Values are reported as relative change from the average of all samples for each phenotype with red = positive relative change, black = no difference, green = negative relative change, and gray = no data available. Dose groups are indicated by the color bar below the sample cluster with blue = 0 mg, purple = 5 mg, and yellow = 10 mg. Separate clusters are defined by a, b, c, and d. Abbreviations: TLS, total lung score; Peri, perivasculitis and peribronchitis; Alv, alveolitis; BALF cell, bronchial alveolar lavage fluid (BALF) total cell number; BALF Prot, BALF protein levels; LDH, lactate dehydrogenase (LDH) activity; SPW, spleen weight; ANA12, anti-nuclear antibody (ANA) score after 12 weeks of exposure; ENA5, designed for the detection of anti-Sm, -RNP, -SS-A (60 kDa and 52 kDa), -SS-B, and -Scl-70 IgG antibodies; RNP, anti-RNP IgG; Sm, anti-Sm IgG; SSA, anti-SSA IgG; SSB, anti-SSB IgG; dsDNA, anti-dsDNA IgG; Chrom, anti-chromatin IgG, ANA4, ANA score after 4 weeks of exposure; ANA8, ANA score after 8 weeks of exposure; ANAPre, ANA score before exposure; BW, body weight; GN, glomerulonephritis; ProtStrip, urine protein using ChemStrip assay.