Article Figures & Data
Figures
- Figure 1.
Human leukemia and lymphoma-associated genes with opposite correlations with biomarkers between male and female newborns. Only the top 4, based on deltaCC are presented; for complete lists refer to Supplementary Table S4. * indicates a significant correlation, with an unadjusted P value less than 0.05. ** indicates the query terms used to search the GO term annotations for each gene.
Tables
- Table 1.
Characteristics of the study population (A), RIN and bench time (B), and data distribution of the various parameters (C)
A All Males Females N 111 45 66 Birth weight 3629 ± 434 3722 ± 416 3564 ± 438 Gestation 39.8 ± 1.1 39.9 ± 1.1 39.7 ± 1.1 Age Mother 31.3 ± 4.2 31.0 ± 4.3 31.5 ± 4.2 Father 32.8 ± 6.4 32.3 ± 4.3 33.7 ± 5.7 Mother BMI BP 23.4 ± 3.9 23.1 ± 3.6 23.6 ± 4.1 Mother was pregnant before no 35% 34% 36% yes 65% 66% 64% Mother smoked BP no 84% 82% 85% occasional 9% 11% 8% daily 7% 7% 6% Delivery start Spontaneous 81% 86% 77% Induced 12% 7% 16% Caesarean section 7% 7% 8% Caesarean sections Planned 7 2 5 Emergency 7 4 3 B RIN (0–10) 8.0 ± 1.3 7.98 ± 1.30 7.97 ± 1.30 Bench time 77.8 ± 172.4 58.77 ± 116.66 90.63 ± 201.29 C DR CALUX 36.4± 9.8 (n = 43) 37.4 ± 10.5 (n = 14) 35.9 ± 9.6 (n = 29) ERα CALUX 15.6 ± 14.4 (n = 34) 16.1 ± 10.6 (n = 17) 15.2 ± 17.8 (n = 17) AR CALUX 0.08 ± 0.06 (n = 31) 0.07 ± 0.03 (n = 16) 0.09 ± 0.08 (n = 15) AA Hb-adducts 16.5 ± 6.6 (n = 84) 16.0 ± 7.1 (n = 34) 16.7 ± 6.4 (n = 50) GA Hb-adducts 10.0 ± 4.0 (n = 84) 9.5 ± 3.8 (n = 34) 10.3 ± 4.0 (n = 50) ‰MNBN 1.2 ± 0.9 (n = 33) 1.1 ± 0.8 (n = 13) 1.2 ± 0.9 (n = 16) Abbreviation: BP, before pregnancy; RIN, RNA integrity number; Bench time, time from blood collection to RNA stabilization.
Data are presented as mean ± SD unless stated otherwise. Birth weight expressed in g, gestation in weeks, age in years, bench time in minutes, DR CALUX in pg TEQ/gr fat, ERα CALUX (ng EEQ/mL plasma), AR CALUX (ng AEQ/mL plasma), Hb-adducts in pmol/g Hb, ‰MNBN in MN per 1,000 binucleated cells.
- Table 2.
Numbers of genes correlating with CALUX, Hb-adducts, and micronuclei
No. of genes Pos. correlation Neg. correlation Gender No. of genes Pos. correlation Neg. correlation Overlap boys-girls DR CALUX 3 0 3 Boys (n = 14) 371 163 208 1 Girls (n = 29) 39 29 10 ERα CALUX 20 14 6 Boys (n = 17) 493 311 182 3 Girls (n = 17) 626 459 167 AR CALUX 83 69 14 Boys (n = 16) 1293 946 347 29 Girls (n = 15) 508 366 142 AA Hb-adducts 0 0 0 Boys (n = 34) 23 18 5 0 Girls (n = 50) 0 0 0 GA Hb-adducts 0 0 0 Boys (n = 34) 6 2 4 0 Girls (n = 50) 0 0 0 ‰MNBN 22 4 18 Boys (n = 13) 1397 662 735 1 Girls (n = 16) 95 28 67 Numbers are presented for sexes grouped together and separately, correlation coefficients more than 0.60 or less than -0.60, and an unadjusted P value ≤ 0.05.
- Table 3.
The GO terms, pathways, and networks enriched among the significantly correlating genes for the various biomarkers for males
GO term/Pathway/Network # significant processes (CC ≥ 0.60/CC ≥ 0.75) P-value (# genes affected/total # in pathway) Database DR CALUX 29/16 Cell cycle 3.76E-04 (31/679) GO Apoptosis 5.63E-04 (26/543) GO ERα CALUX 50/9 Antigen processing and presentation 2.92E-05 (9/61) GO Regulation of adaptive immune response 1.69E-04 (8/60) GO AR CALUX 7/1 Cell cycle_G1-S 6.64E-03 (17/122) Pathways Proteolysis_Ubiquitin–proteasomal proteolysis 7.11E-03 (19/143) Pathways AA Hb-adducts 4/0 Regulation of developmental process 5.51E-03 (4/637) GO Regulation of T-cell activation 8.89E-03 (2/121) GO GA Hb-adducts 0/0 ‰MNBN 22/53 DNA damage_Checkpoint 9.22E-03 (16/92) Networks Regulation of cell cyclea 3.49E-04 (14/314) GO Apoptosis and survival_p53-dependent apoptosisa 1.06E-03 (4/25) Pathways Only processes mentioned in the text are presented; for complete lists refer to Supplementary data Table S1.
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↵aFound when using the 0.75 correlation coefficient cut-off.
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- Table 4.
The GO terms, pathways, and networks enriched for males among the significantly correlating genes for the various biomarkers for females
GO term/Pathway/Network # Significant Processes (CC ≥ 0.60/CC ≥ 0.75) P-Value (# Genes Affected/Total # in Pathway) Database DR CALUX 18/0 Nucleosome assembly 1.22E-05 (4/69) GO Cell cycle_Initiation of mitosis 6.37E-03 (2/18) Pathways ERα CALUX 74/88 Immune system process 8.49E-06 (58/863) GO Regulation of lymphocyte activation 1.99E-05 (18/155) GO AR CALUX 39/33 Translational elongation 8.72E-19 (28/104) GO Ubiquitin-dependent protein catabolic process 4.70E-06 (21/214) GO AA Hb-adducts 0/0 GA Hb-adducts 0/0 ‰MNBN 3/6 Nucleotide-excision repair, DNA damage removal 1.30E-04 (3/18) GO Cell cycle_Initiation of mitosis 6.37E-03 (2/18) Pathways Only processes mentioned in the text are presented; for complete lists refer to Supplementary data Table S2.
- Table 5.
GO terms and pathways enriched for males among all correlating genes using Tox-Profiler
Biomarker Process # Significant Processes Males/Females T-Value Males P-Value Males T-Value Females P-Value Females Database DR CALUX 5/29 Nucleosome assembly 4.1 0.154 6.4 <0.001 GO T-cell receptor signaling pathway −2.7 1.000 −4.5 0.001 KEGG B-cell receptor signaling pathway −0.6 1.000 −4.1 0.005 KEGG TNF-alpha-NF-kB Signaling Pathway 2.9 0.551 −4.2 0.010 WikiPathways ERα CALUX 2/41 Immune response −1.4 1.000 6.8 <0.001 GO T-cell receptor signaling pathway −1.5 1.000 6.8 <0.001 WikiPathways B-cell receptor signaling pathway −1.9 1.000 4.9 <0.001 WikiPathways AR CALUX 12/24 Immune response −2.5 1.000 −6.6 <0.001 GO Ubiquitin-dependent protein catabolic process 0.9 1.000 5.9 <0.001 GO Nucleosome −4.7 0.020 −1.2 1.000 GO AA Hb-adducts 4/17 Translational elongation −1.7 1.000 8.8 <0.001 GO RNA splicing −5.6 <0.001 1.7 1.0000 GO GA Hb-adducts 8/12 Wnt signaling pathway 4.2 0.032 0.2 1.000 KEGG ‰MNBN 30/13 Translational elongation 8.5 <0.001 −5.7 <0.001 GO Spliceosome 4.6 0.002 −5.4 <0.001 KEGG mRNA processing 4.0 0.012 −4.1 0.002 WikiPathways Pathways in cancer 4.8 0.001 1.8 1.000 KEGG Translational elongation 8.5 <0.001 −5.7 <0.001 GO Only processes mentioned in the text are presented; for complete lists refer to Supplementary data Table S3.
Supplementary Data
Files in this Data Supplement:
- Supplementary Table 1 - PDF file, 32K, Complete list of GO terms, pathways and networks enriched among the significantly correlating genes for the various biomarkers for males.
- Supplementary Table 2 - PDF file, 35K, Complete list of GO terms, pathways and networks enriched among the significantly correlating genes for the various biomarkers for females.
- Supplementary Table 3 - PDF file, 40K, Complete list of GO terms, pathways and networks enriched among the significantly correlating genes using Tox-Profiler.
- Supplementary Table 4 - PDF file, 67K, Complete list of Human leukemia and lymphoma associated genes showing opposite correlations with biomarkers between male and female newborns.
Volume 21, Issue 10
