Additional file 1 of Protein interaction networks provide insight into fetal origins of chronic obstructive pulmonary disease
Creators: name: Röhl, Annika
name: Baek, Seung Han
name: Kachroo, Priyadarshini
name: Morrow, Jarrett D.
name: Tantisira, Kelan
name: Silverman, Edwin K.
name: Weiss, Scott T.
name: Sharma, Amitabh
name: Glass, Kimberly
name: DeMeo, Dawn L.
Publisher: name: figshare
Year: 2022
Subjects: subject: Medicine
subject: Cell Biology
subject: Genetics
subject: FOS: Biological sciences
subject: Biotechnology
subject: 69999 Biological Sciences not elsewhere classified
subject: Cancer
subject: Science Policy

description: Additional file 1: Figure S1. The overlap of the significant genes from the different data sets. Figure S2. Schema for the approach. Based on a set of p-value cutoffs the method computes for each cutoff the largest connected component (LCC) given by all genes which have a p-value smaller than the cutoff. Next, for each LCC, its size (number of nodes) is compared against random expectation and a corresponding z-score is computed. The LCC with a z-score higher than 1.6 and containing genes with low p-values is considered to be the disease module. Figure S3-S5. The p-value cutoffs of the genes are given on the x-axis and the z-scores on the y-axis. For each p-value cutoff a LCC is computed using all genes of p-value lower than the cutoff. For this LCC a z-score is computed, using randomization. The z-scores are illustrated by the red dots. All details on the results can be found in the Table S8. Figure S3. Computation of the fetal lung methylation module. The module for the fetal lung methylation data set has a z-score of 2.86 at a p-value cutoff for the genes of 0.003. 265 genes in the data set have a p-value lower than this cut-off and they give a LCC of size 50, which is the exposure module for the fetal lung methylation data set. The size of the LCC given for all genes which have a p-value smaller than 0.01 is 289, therefore already too large for a reasonable disease module and therefore we did not consider higher p-value cutoffs. Figure S4. Computation of the COPD methylation module. The module for the COPD methylation data set has a z-score of 2.034 and the p-value cutoff for the genes is 0.037. 268 genes in the data set have a lower p-value than this cutoff and they give a LCC of size 37, which is the disease module for the COPD methylation data set. Figure S5. Computation of the COPD expression module. The module for the COPD expression data set has a z-score of 9.7 and is given by all genes which are significantly differentially expressed, thus which have a p-value lower than 0.05. They give a LCC of size 64, which is the disease module for the COPD expression data set. Figure S6-S7. Computation of the module using genes which are mapped to nominally differentially methylated CpG sites in both data sets: The p-value cutoffs of the genes are given on the x-axis and the z-scores on the y-axis. For each p-value cutoff a LCC is computed using all genes of p-value lower than the cut-off. For this LCC a z-score is computed, using randomization. The z-scores are illustrated by the red dots. All details on the results can be found in the Table S8. Figure S6. Using p-values from the fetal lung methylation data set: The module using p-values from the fetal lung methylation data set has a z-score of 3.2 at a p-value cutoff for the genes of 0.01. 202 genes in the data set have a p-value lower than this cut-off and they give a LCC of size 35. Figure S7. Using p-values from the COPD methylation data set: The module using p-values from the adult COPD patients methylation data set has a z-score of 2.2 at a p-value cutoff for the genes of 0.04. 248 genes in the data set have a p-value lower than this cut-off and they give a LCC of size 50. Figure S8-S9. Overlap modules: Using the 502 genes which are mapped to nominally differentially methylated CpG sites in the fetal lung methylation data set as well as in the COPD methylation data set we computed two modules using the p-values given by one of the data sets resp. The modules have 11 genes in common which are highlighted in red. Figure S8. Overlap module using fetal lung p-values: The module consists of 35 genes, where 11 of them can be found in the module constructed using the COPD p-values as well (highlighted in red). Figure S9. Overlap module using COPD p-values: The module consists of 50 genes, where 11 of them can be found in the module constructed using the fetal lung p-values as well (highlighted in red).