Combining micro-RNA and protein sequencing to detect robust biomarkers for Graves' disease and orbitopathy

Scientific Reports
Lei ZhangFilippo Biscarini

Abstract

Graves' Disease (GD) is an autoimmune condition in which thyroid-stimulating antibodies (TRAB) mimic thyroid-stimulating hormone function causing hyperthyroidism. 5% of GD patients develop inflammatory Graves' orbitopathy (GO) characterized by proptosis and attendant sight problems. A major challenge is to identify which GD patients are most likely to develop GO and has relied on TRAB measurement. We screened sera/plasma from 14 GD, 19 GO and 13 healthy controls using high-throughput proteomics and miRNA sequencing (Illumina's HiSeq2000 and Agilent-6550 Funnel quadrupole-time-of-flight mass spectrometry) to identify potential biomarkers for diagnosis or prognosis evaluation. Euclidean distances and differential expression (DE) based on miRNA and protein quantification were analysed by multidimensional scaling (MDS) and multinomial regression respectively. We detected 3025 miRNAs and 1886 proteins and MDS revealed good separation of the 3 groups. Biomarkers were identified by combined DE and Lasso-penalized predictive models; accuracy of predictions was 0.86 (±0:18), and 5 miRNA and 20 proteins were found including Zonulin, Alpha-2 macroglobulin, Beta-2 glycoprotein 1 and Fibronectin. Functional analysis identified relevant meta...Continue Reading

References

Oct 5, 1990·Journal of Molecular Biology·S F AltschulD J Lipman
Aug 1, 1990·The British Journal of Ophthalmology·S E Feldon, L Levin
Nov 1, 1986·The Histochemical Journal·J G WoodL Napier-Marshall
Nov 1, 1994·Digestive Diseases and Sciences·S NaveauJ C Chaput
Apr 15, 2005·Toxicological Sciences : an Official Journal of the Society of Toxicology·Danitsja M van LeeuwenJoost H M van Delft
Jul 13, 2006·The Journal of Clinical Endocrinology and Metabolism·Anja K EcksteinNils G Morgenthaler
Oct 13, 2006·Archives of Ophthalmology·Glynn R C BakerMarian Ludgate
Oct 24, 2006·Carcinogenesis·Danitsja M van LeeuwenJoost H M van Delft
Aug 3, 2007·The Journal of Clinical Investigation·George A Calin, Carlo M Croce
Jan 29, 2008·Brain : a Journal of Neurology·Mikhail BogdanovM Flint Beal
Mar 18, 2008·Thyroid : Official Journal of the American Thyroid Association·Luigi BartalenaWilmar M Wiersinga
Aug 23, 2008·Endocrinology·Syed A MorshedTerry F Davies
Sep 9, 2008·Cell·Elaine HolmesJeremy K Nicholson
Jan 20, 2009·Clinical Pharmacology and Therapeutics·R H Glassman, M J Ratain
May 23, 2009·The Journal of Endocrinology·Lei ZhangMarian Ludgate
Jul 25, 2009·Oral Diseases·A MichaelI Alevizos
Apr 27, 2010·Nature Genetics·UNKNOWN Tobacco and Genetics Consortium
Sep 14, 2011·Nucleic Acids Research·Marc R FriedländerNikolaus Rajewsky
Dec 14, 2011·The Journal of Clinical Endocrinology and Metabolism·Lei ZhangMarian Ludgate
Feb 11, 2012·British Journal of Clinical Pharmacology·Nazeeha HasanPankaj Sharma
Mar 20, 2012·Translational Research : the Journal of Laboratory and Clinical Medicine·Rekha Vij, Imre Noth
Mar 30, 2012·The Journal of Clinical Endocrinology and Metabolism·Rongjiao LiuShu Wang
May 29, 2012·Best Practice & Research. Clinical Endocrinology & Metabolism·John H Lazarus
Aug 10, 2012·Thyroid : Official Journal of the American Thyroid Association·Nina MatheisGeorge J Kahaly
Apr 16, 2013·Clinical Endocrinology·Wilmar M Wiersinga
Jul 23, 2013·Chest·Alborz Hakimi ShokiBradley S Quon
Aug 22, 2013·Journal of Computational Biology : a Journal of Computational Molecular Cell Biology·Steven N HartJean-Pierre Kocher
Feb 4, 2014·Genome Biology·Charity W LawGordon K Smyth
Apr 4, 2014·Bioinformatics·Anthony M BolgerBjoern Usadel
Feb 6, 2015·Genetics, Selection, Evolution : GSE·Stefano BiffaniFilippo Biscarini
Apr 2, 2015·Investigative Ophthalmology & Visual Science·Nina MatheisGeorge J Kahaly
May 2, 2015·Frontiers in Plant Science·Luigi Lucini, Letizia Bernardo
Jun 4, 2015·The British Journal of Ophthalmology·James T RosenbaumStephen R Planck
Dec 15, 2015·Advances in Experimental Medicine and Biology·Jan NovákGaetano Santulli
Feb 27, 2016·International Journal of Medical Sciences·Fang PengDayong Gu

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Citations

Apr 10, 2020·Endocrinology·Liang YinJie Shen
Nov 22, 2019·Frontiers in Molecular Biosciences·Kuldeep DhamaSunil Kumar Joshi
Jun 17, 2020·Experimental and Clinical Endocrinology & Diabetes : Official Journal, German Society of Endocrinology [and] German Diabetes Association·Nele FriedrichUwe Völker
Mar 3, 2021·Best Practice & Research. Clinical Endocrinology & Metabolism·Camilla ViriliMarco Centanni
Jan 30, 2021·European Thyroid Journal·Giulia Masetti, Marian Ludgate

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Methods Mentioned

BETA
proteomic profiling
proteomics sequencing
PCR
Protein Assay
electrophoresis
Chip
MDS

Software Mentioned

sim
protDE
ggplot2
R environment
Fastq
FastQC
Python
qvalue
NB
R package

Related Concepts

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