Exposure to livestock in the study population.

<p>Case (P-ADC) and control (non-P-ADC) groups were compared using univariate analysis with the Chi-2 test.</p

Factors independently associated with pneumonic-type lung adenocarcinoma.

<p>Multivariate analysis was performed using log regression model including significant variables at univariate analysis with <i>p</i><0.15.</p><p>CI: Confidence Interval.</p

Additional file 1 of Blood MMP-9 measured at 2 years after lung transplantation as a prognostic biomarker of chronic lung allograft dysfunction

Additional file 1: S1. COLT study protocol. S2. Description of variables of interest. Figure S1. Study protocol. Figure S2. Comparison of MMP-9 blood levels of Y2 analysis according to CLAD phenotypes. Figure S3. Precision-Recall (A) and ROC (B) curves for the Y1 MMP-9 analysis. Figure S4. Comparison of MMP-9 blood levels of Y2 analysis according to CLAD phenotypes. Figure S5. Longitudinal analysis of MMP-9 blood levels for recipients with available samples before transplantation, at Y1 and Y2

Characterization of under-expressed genes in the CRD signature.

<p>A) Tree analysis of the CRD signature. Identification of the most representative genes by Gominer, PAM, IPA analysis and validation of the candidate genes in the validation cohort by qPCR; B) Network generated by IPA on the most significant GO categories in the CRD signature. Solid lines indicate <i>direct</i> interactions and dashed lines represent <i>indirect</i> interactions. Under-expressed genes in CRD are in gray. C) PAM analysis based on the most representative GO categories of Cluster A and B. Green represents relatively low expression, and red indicates relatively high expression. D) List of 9 genes able to classify correctly CRD and HC. E) The PCA graph of the 9 genes identified by PAM analysis indicated a clear separation between HC and patients with CRD (CF and PAH).</p

Validation of the most representative genes in the validation cohort.

<p>A) Quantitative PCR validation of 3 genes from the PAM analysis (<i>IL-7R</i>, <i>TCF-7</i> and <i>CD6</i>) using the validation cohort; B) based on these qPCR values, <i>IL-7R</i> and <i>TCF-7</i> enabled good discrimination between patients with CRD and HC, according to a receiver operating characteristic (ROC) analysis (AUC = 89.6% with p<0.001 and AUC = 89.4% with p<0.001, respectively); C) Median intensity fluorescence (MFI) and mRNA expression of <i>IL-7R</i> in PBMCs from healthy controls (HC) cultivated 12 hours under hypoxic and normoxic condition; D) MFI of IL-7R on PBMCs from CRD patients compared to HC; E) <i>TCF-7</i> expression in PBMCs from HC under hypoxia or normoxia.</p

Gominer Analysis based for over-expressed genes in CF signature versus HC.

<p>Only GO categories enriched in cluster D (A) and in cluster E (B) with FDR less than 1%, with enrichment superior to 2 and with more than 10 genes are displayed.</p><p>Gominer Analysis based for over-expressed genes in CF signature versus HC.</p

Unsupervised hierarchical clustering analysis.

<p>A) Tree analysis. Clustering analysis based on the 30,146 probes corresponding to 17,163 unique genes expressed in PAH, CF patients and Healthy Controls (HC). 3 signatures were found: 1 common between CF and PAH (named CRD signature), 1 specific to CF and 1 to PAH; B) Principal Component Analysis (PCA) displayed a clear separation between HC and patients with CRD, whereas CF and PAH patients were less distinct; C) 5 groups of genes (or clusters) were selected, A to E, based on a combined approach: selected genes were clustered together and exhibited a t-test p-value below 1% between the CRD group (PAH+CF), CF or PAH versus HC. Green represents relatively low expression, and red indicates relatively high expression.</p

Gominer Analysis based for over-expressed genes in PAH signature versus HC.

<p>Only GO categories enriched in cluster C with FDR less than 1%, with enrichment superior to 2 and with more than 10 genes are displayed.</p><p>Gominer Analysis based for over-expressed genes in PAH signature versus HC.</p

Characterization of over-expressed genes in the PAH signature.

<p>A) Tree analysis of the PAH signature. Identification of the most representative genes by Gominer, PAM, IPA analysis and validation by qPCR of the candidate genes in the validation cohort; B) Network generated by IPA on the most significant GO categories in PAH signature. Over-expressed genes in PAH are in gray. C) PAM analysis based on the cluster, <i>Green</i> represents relatively low expression, and <i>red</i> indicates relatively high expression; D and E) Validation by qPCR of <i>MDK</i> and <i>LGALS3</i> in the validation cohort, respectively.</p

Strategy for selecting patients from the COLT (COhort of Lung Transplantation).

<p>*Emphysema, Sarcoïdosis, Lymphangiomatosis, Secondary PAH, histiocytosis, fibrosis, bronchiectasis and COPD (Chronic Obstructive Pulmonary Disease). CF: Cystic Fibrosis; PAH: Pulmonary Arterial hypertension; COPD: Chronic Obstructive Pulmonary Disease. Patients were excluded during the RNA process following specific qualities criteria.</p