EGAGenomicsIllumina HiSeq 2000Otherhttps://ega-archive.org/studies/EGAS00001000962EGAEGA study EGAS00001000962Cancer-associated genome-wide hypomethylation and copy number aberrationsEGArestrictedWe performed a high-resolution analysis of the biological characteristics of plasma DNA in systemic lupus erythematosus (SLE) patients using massively parallel genomic and methylomic sequencing. A number of plasma DNA abnormalities were found. First, aberrations in measured genomic representations (MGRs) were identified in the plasma DNA of SLE patients. The extent of the aberrations in MGRs correlated with anti-double-stranded DNA (anti-dsDNA) antibody level. Second, the plasma DNA of active SLE patients exhibited skewed molecular size-distribution profiles with a significantly increased proportion of short DNA fragments. The extent of plasma DNA shortening in SLE patients correlated with the SLE disease activity index (SLEDAI) and anti-dsDNA antibody level. Third, the plasma DNA of active SLE patients showed decreased methylation densities. The extent of hypomethylation correlated with SLEDAI and anti-dsDNA antibody level. To explore the impact of anti-dsDNA antibody on plasma DNA in SLE, a column-based protein G capture approach was used to fractionate the IgG-bound and non-IgG-bound DNA in plasma. Compared with healthy individuals, SLE patients had higher concentrations of IgG-bound DNA in plasma. More IgG binding occurs at genomic locations showing increased MGRs. Furthermore, the IgG-bound plasma DNA was shorter in size and more hypomethylated than the non-IgG-bound plasma DNA. These observations have enhanced our understanding of the spectrum of plasma DNA aberrations in SLE and may provide new molecular markers for SLE. Our results also suggest that caution should be exercised when interpreting plasma DNA-based noninvasive prenatal testing and cancer testing conducted for SLE patients.Plasma DNA aberrations in systemic lupus erythematosus revealed by genomic and methylomic sequencing.Chan Rebecca W Y RW, Jiang Peiyong P, Peng Xianlu X, Tam Lai-Shan LS, Liao Gary J W GJ, Li Edmund K M EK, Wong Priscilla C H PC, Sun Hao H, Chan K C Allen KC, Chiu Rossa W K RW, Lo Y M Dennis YMextent, Fresh, malignant Growth, other disease, lupus erythematosus, DNS, Fresh Frozen Plasma, Activity, determination, (Deoxyribonucleotide)n, SLE, Sle, Blood, cell type cancer, Prenatal, number, B-cell receptor complex, protein, congenital defects, protein-containing complex, Ximpact, supernumerary, aplasia, Deoxyribonucleic acids, SLE - lupus erythematosus, antibody, protein polypeptide chains, Readability, BCR complex, cfDNA Screening, Client., Deoxyribonucleic Acid, diseases, reduced, polypeptide chain, subnumerary, disease or disorder, diseases and disorders, Prenatal Cell-Free DNA Screening, defects, protein aggregate, immunoglobulin complex, present in fewer numbers in organism, neoplasm, malignant tumour, systemic, Fresh Frozen Plasmas, Fresh Frozen, increased, Blood Plasma, proportion, thymus nucleic acid, human disease, CG12918, pattern, membrane bound, distribution, neoplasm (disease), hypoplasia, stubby, Noninvasive Prenatal Screening, Double Stranded, Deoxyribonucleic acid, proteins, Prenatal Cell Free DNA Screening, number of, decreased number, systemic lupus erythematosus (disease), DmelCG12918, CA, non-neoplastic, decreased, systemic lupus erythematosus susceptibility to, column, Prenatal Testing, Noninvasive Prenatal Diagnosis, malignant neoplasm, Clients, Blood Plasmas, has or lacks parts of type, disorder, s, Homo sapiens disease, Double-Stranded DNA, (Deoxyribonucleotide)m, deoxyribonucleic acids, DNAn, B-lymphocyte receptor complex, Methylations, plasma, ratio, malignancy, Frozen Plasma, Prenatal Screening, completeness, protein complex, malignant, DNAn+1, disorders, Systemic lupus erythematosus, extra or missing physical or functional parts, medical condition, Double-Stranded, antibodies, Plasmas, disseminated lupus erythematosus, Client, deformities, impact-a, results, (Deoxyribonucleotide)n+m, mereological quality, Frozen Plasmas, shortened, MT, native protein, natural protein, agenesis, excess LMW-DNA, malignant neoplasm (disease), chemical analysis, Protein, Diseases, organ system cancer, condition, methylation, ds-DNA, desoxyribose nucleic acid, lupus nephritis, Prenatal cfDNA Screening, excess lymphocyte low molecular weight DNA, opsonin activity, Plasma, atresia, portion of blood plasma, primary cancer, IgG, increased number, susceptibility to, malformations, proportionality, systemic lupus erythematosus, portion of plasma, rate, Understanding, malignant tumor, Noninvasive, present in greater numbers in organism, disease, blood plasm, immunoglobulin, Prenatal Diagnosis, B cell receptor accessory molecule complex, Patient, malignant neoplastic disease, Indexes, birth defects, anomalies, ds DNA, cardinality, B lymphocyte receptor complex, Desoxyribonukleinsaeure, B cell receptor activity, quotient, assay, DNA, short, E430016J11Rik, cancer, General activity, RWDD5, accessoryPlasma, Fresh, systemic, Fresh Frozen Plasmas, Fresh Frozen, portion of blood plasma, Blood Plasma, thymus nucleic acid, lupus erythematosus, Frozen Plasma, DNS, Fresh Frozen Plasma, (Deoxyribonucleotide)n, SLE, Blood, DNAn+1, susceptibility to, systemic lupus erythematosus, Systemic lupus erythematosus, portion of plasma, Double Stranded, Deoxyribonucleic acid, Double-Stranded, Plasmas, disseminated lupus erythematosus, systemic lupus erythematosus (disease), Deoxyribonucleic acids, (Deoxyribonucleotide)n+m, SLE - lupus erythematosus, Frozen Plasmas, blood plasm, systemic lupus erythematosus susceptibility to, Deoxyribonucleic Acid, Blood Plasmas, excess LMW-DNA, excess lymphocyte low molecular weight DNA., ds DNA, Desoxyribonukleinsaeure, Double-Stranded DNA, (Deoxyribonucleotide)m, DNA, deoxyribonucleic acids, DNAn, ds-DNA, desoxyribose nucleic acid, lupus nephritis, plasmaextent, Fresh, malignant Growth, other disease, lupus erythematosus, DNS, Fresh Frozen Plasma, Activity, determination, (Deoxyribonucleotide)n, SLE, Sle, Blood, cell type cancer, Prenatal, number, B-cell receptor complex, protein, congenital defects, protein-containing complex, Ximpact, supernumerary, aplasia, Deoxyribonucleic acids, SLE - lupus erythematosus, antibody, protein polypeptide chains, Readability, BCR complex, cfDNA Screening, Client., Deoxyribonucleic Acid, diseases, reduced, polypeptide chain, subnumerary, disease or disorder, diseases and disorders, Prenatal Cell-Free DNA Screening, defects, protein aggregate, immunoglobulin complex, present in fewer numbers in organism, neoplasm, malignant tumour, systemic, Fresh Frozen Plasmas, Fresh Frozen, increased, Blood Plasma, proportion, thymus nucleic acid, human disease, CG12918, pattern, membrane bound, distribution, neoplasm (disease), hypoplasia, stubby, Noninvasive Prenatal Screening, Double Stranded, Deoxyribonucleic acid, proteins, Prenatal Cell Free DNA Screening, number of, decreased number, systemic lupus erythematosus (disease), DmelCG12918, CA, non-neoplastic, decreased, systemic lupus erythematosus susceptibility to, column, Prenatal Testing, Noninvasive Prenatal Diagnosis, malignant neoplasm, Clients, Blood Plasmas, has or lacks parts of type, disorder, s, Homo sapiens disease, Double-Stranded DNA, (Deoxyribonucleotide)m, deoxyribonucleic acids, DNAn, B-lymphocyte receptor complex, Methylations, plasma, ratio, malignancy, Frozen Plasma, Prenatal Screening, completeness, protein complex, malignant, DNAn+1, disorders, Systemic lupus erythematosus, extra or missing physical or functional parts, medical condition, Double-Stranded, antibodies, Plasmas, disseminated lupus erythematosus, Client, deformities, impact-a, results, (Deoxyribonucleotide)n+m, mereological quality, Frozen Plasmas, shortened, MT, native protein, natural protein, agenesis, excess LMW-DNA, malignant neoplasm (disease), chemical analysis, Protein, Diseases, organ system cancer, condition, methylation, ds-DNA, desoxyribose nucleic acid, lupus nephritis, Prenatal cfDNA Screening, excess lymphocyte low molecular weight DNA, opsonin activity, Plasma, atresia, portion of blood plasma, primary cancer, IgG, increased number, susceptibility to, malformations, proportionality, systemic lupus erythematosus, portion of plasma, rate, Understanding, malignant tumor, Noninvasive, present in greater numbers in organism, disease, blood plasm, immunoglobulin, Prenatal Diagnosis, B cell receptor accessory molecule complex, Patient, malignant neoplastic disease, Indexes, birth defects, anomalies, ds DNA, cardinality, B lymphocyte receptor complex, Desoxyribonukleinsaeure, B cell receptor activity, quotient, assay, DNA, short, E430016J11Rik, cancer, General activity, RWDD5, accessoryPlasma, Fresh, systemic, Fresh Frozen Plasmas, Fresh Frozen, portion of blood plasma, Blood Plasma, thymus nucleic acid, lupus erythematosus, Frozen Plasma, DNS, Fresh Frozen Plasma, (Deoxyribonucleotide)n, SLE, Blood, DNAn+1, susceptibility to, systemic lupus erythematosus, Systemic lupus erythematosus, portion of plasma, Double Stranded, Deoxyribonucleic acid, Double-Stranded, Plasmas, disseminated lupus erythematosus, systemic lupus erythematosus (disease), Deoxyribonucleic acids, (Deoxyribonucleotide)n+m, SLE - lupus erythematosus, Frozen Plasmas, blood plasm, systemic lupus erythematosus susceptibility to, Deoxyribonucleic Acid, Blood Plasmas, excess LMW-DNA, excess lymphocyte low molecular weight DNA., ds DNA, Desoxyribonukleinsaeure, Double-Stranded DNA, (Deoxyribonucleotide)m, DNA, deoxyribonucleic acids, DNAn, ds-DNA, desoxyribose nucleic acid, lupus nephritis, plasma0.00.00.00.00.0falsePlasma DNA aberrations in systemic lupus erythematosus revealed by genomic and methylomic sequencingWe performed a high-resolution analysis of the biological characteristics of plasma DNA in systemic lupus erythematosus (SLE) patients using massively parallel genomic and methylomic sequencing. A number of plasma DNA abnormalities were found. First, aberrations in measured genomic representations (MGRs) were identified in the plasma DNA of SLE patients. The extent of the aberrations in MGRs correlated with anti-double–stranded DNA (anti-dsDNA) antibody level. Second, the plasma DNA of active SLE patients exhibited skewed molecular size-distribution profiles with a significantly increased proportion of short DNA fragments. The extent of plasma DNA shortening in SLE patients correlated with the SLE disease activity index (SLEDAI) and anti-dsDNA antibody level. Third, the plasma DNA of active SLE patients showed decreased methylation densities. The extent of hypomethylation correlated with SLEDAI and anti-dsDNA antibody level. To explore the impact of anti-dsDNA antibody on plasma DNA in SLE, a column-based protein G capture approach was used to fractionate the IgG-bound and non–IgG-bound DNA in plasma. Compared with healthy individuals, SLE patients had higher concentrations of IgG-bound DNA in plasma. More IgG binding occurs at genomic locations showing increased MGRs. Furthermore, the IgG-bound plasma DNA was shorter in size and more hypomethylated than the non–IgG-bound plasma DNA. These observations have enhanced our understanding of the spectrum of plasma DNA aberrations in SLE and may provide new molecular markers for SLE. Our results also suggest that caution should be exercised when interpreting plasma DNA-based noninvasive prenatal testing and cancer testing conducted for SLE patients.2017-07-26 15:39:27EGAS00001000962960625427797EGAD00001001093EGAC00001000078