Top networks, related disorders and diseases identified in NTD case, controls and known NTD candidate genes.

<p>Top networks, related disorders and diseases identified in NTD case, controls and known NTD candidate genes.</p

Summary of whole genomic copy number variants (CNVs) in the two groups; Wilcoxon rank-sum test was used for statistical analysis.

<p><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0054492#pone-0054492-g001" target="_blank">Figure 1A:</a> Distribution of all called genomic CNVs by size. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0054492#pone-0054492-g001" target="_blank">Figure 1B:</a> Distribution of all called genomic CNVs by frequency.</p

The detailed phenotypes in 11 systemic NTDs carrying ciliogenic CNVs and abnormal urinary/adrenal development.

<p>The detailed phenotypes in 11 systemic NTDs carrying ciliogenic CNVs and abnormal urinary/adrenal development.</p

Comparison of non-DGV CNVs, non-DGV genic CNVs and ciliogenic CNVs in NTD cases and controls.

*<p>For sample with both deletion and duplication, we counted twice times, It was same for genic CNVs and ciliogenic CNVs;</p>**<p>Logistical regression analysis among different CNVs and NTDs;</p>***<p>Lower <i>p</i> value in non-DGV genic CNVs and ciliogenic CNVs compared with non-DGV CNVs;</p

The general characteristics of the NTD cohort.

*<p>p = 0.650, compared to controls including 39 male and 36 female.</p

The Relationship of NTDs categories with non-DGV ciliogenic CNVs.

*<p>compared with cranial NTDs, two-tailed;</p>**<p>compared with systemic NTDs, two-tailed;</p>***<p>compared with systemic NTDs with abnormal urinary/adrenal gland development, one-tailed.</p

Top bio-functional networks in known NTD candidate genes.

<p>Pathways analysis identified “<i>Organ Development, Embryonic Development, Tissue Development</i>” in 223 known NTD candidate genes after literatures review. The known signaling pathways for neural tube closure including BMP signaling, SHH and Wnt/β-catenin signaling interact with two novel pathways in NTD-affected cases (CP in the oval regions).</p

Classification of diffuse parenchymal lung diseases in children (chDPLD).

<p>ANCA: Antineutrophil cytoplasmic antibodies;</p><p>SLE: Systemic lupus erythematosus;</p><p>AIDS: Acquired immune deficiency syndrome.</p><p>Classification of diffuse parenchymal lung diseases in children (chDPLD).</p

The clinico-radiologic-pathologic data of children with diffuse parenchymal lung diseases (chDPLD).

<p>F, female; M, male; m, months; RVD, restrictive ventilatory dysfunction; MVD, mixed ventilatory dysfunction; GGO, ground glass opacity; PAP, pulmonary alveolar proteinosis; EAA, extrinsic allergic alveolitis; PAM, pulmonary alveolar microlithiasis; AIP, acute interstitial pneumonia; LIP, lymphocytic interstitial pneumonia; NSIP, non-specific interstitial pneumonia; BOOP, bronchiolitis obliterans organizing pneumonia; AIP, acute interstitial pneumonia.</p><p>The clinico-radiologic-pathologic data of children with diffuse parenchymal lung diseases (chDPLD).</p

Chest tomography (CT) images and pathology results of several cases.

<p>1A: The CT shows a paving stone sign and air bronchograms in patients with pulmonary alveolar proteinosis (case 2 in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0116930#pone.0116930.t002" target="_blank">Table 2</a>). 1B: Under light microscopy, the case of pulmonary alveolar proteinosis (case 2) shows evidence of periodic acid-Schiff-positive material filling the alveoli. Interstitial cell infiltrates, including lymphocytes and plasma cells with type II cell hyperplasia, are found. 2A: Multiple thin-walled cysts are seen in the subpleural region in the CT image of lipoid pneumonia (case 6). 2B: Light microscopy of lipoid pneumonia (case 6) shows a large amount of cholesterol crystallization in the alveolar spaces with lymphoid follicles in the alveolar septa. 3A: The CT image of non-specific interstitial pneumonia (case 15) shows reticulation on the background of ground glass opacity and interlobular septal thickening. 3B: A typical pathology picture of cellular non-specific interstitial pneumonia (case 15). The lungs are uniformly involved. Interstitial chronic inflammation consists of lymphocytes and plasma cells. 4A: On the background of ground glass opacity, thin-walled cysts are scattered in the lung fields (case 20, lymphocytic interstitial pneumonia). 4B: In case 20, dense interstitial lymphoid infiltrates, including lymphocytes and plasma cells with type II cell hyperplasia, are observed. The alveolar septal interstitium is expanded by fibrosis. Lymphoid follicles are present. 5A: In case 24, a case of acute interstitial pneumonia, a patchy high-density shadow and bronchograms are seen in the CT image. 5B: Case 24 exhibits diffuse alveolar damage by light microscopy. The alveolar septal interstitium is expanded. Fibroblast proliferation and hyaline membrane disease are shown.</p