{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T17:58:01Z","timestamp":1791050281709,"version":"4.1.0"},"reference-count":138,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,4,29]],"date-time":"2021-04-29T00:00:00Z","timestamp":1619654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"PolyU PhD Studentship","award":["RTX2"],"award-info":[{"award-number":["RTX2"]}]},{"name":"RGC General Research Fund","award":["15104819"],"award-info":[{"award-number":["15104819"]}]},{"name":"RGC General Research Fund","award":["15102015\/15M"],"award-info":[{"award-number":["15102015\/15M"]}]},{"name":"Shenzhen Science and Technology Innovation Commission","award":["JCYJ20180507183409601"],"award-info":[{"award-number":["JCYJ20180507183409601"]}]},{"name":"Australian Government Endeavour Cheung Kong Research Fellowship","award":["G0189472 (DYT, SMF)"],"award-info":[{"award-number":["G0189472 (DYT, SMF)"]}]},{"name":"Australian DIIRSE International Science Linkage","award":["CG120160 (SMF)"],"award-info":[{"award-number":["CG120160 (SMF)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Most of the previous myopic animal studies employed a single-candidate approach and lower resolution proteomics approaches that were difficult to detect minor changes, and generated limited systems-wide biological information. Hence, a complete picture of molecular events in the retina involving myopic development is lacking. Here, to investigate comprehensive retinal protein alternations and underlying molecular events in the early myopic stage, we performed a data-independent Sequential Window Acquisition of all Theoretical Mass Spectra (SWATH) based proteomic analysis coupled with different bioinformatics tools in pigmented guinea pigs after 4-day lens-induced myopia (LIM). Myopic eyes compared to untreated contralateral control eyes caused significant changes in refractive error and choroid thickness (p &lt; 0.05, n = 5). Relative elongation of axial length and the vitreous chamber depth were also observed. Using pooled samples from all individuals (n = 10) to build a species-specific retinal ion library for SWATH analysis, 3202 non-redundant proteins (with 24,616 peptides) were identified at 1% global FDR. For quantitative analysis, the 10 individual retinal samples (5 pairs) were analyzed using a high resolution Triple-TOF 6600 mass spectrometry (MS) with technical replicates. In total, 37 up-regulated and 21 down-regulated proteins were found significantly changed after LIM treatment (log2 ratio (T\/C) &gt; 0.26 or &lt; \u22120.26; p \u2264 0.05). Data are accepted via ProteomeXchange with identifier PXD025003. Through Ingenuity Pathways Analysis (IPA), \u201clipid metabolism\u201d was found as the top function associated with the differentially expressed proteins. Based on the protein abundance and peptide sequences, expression patterns of two regulated proteins (SLC6A6 and PTGES2) identified in this pathway were further successfully validated with high confidence (p &lt; 0.05) using a novel Multiple Reaction Monitoring (MRM) assay on a QTRAP 6500+ MS. In summary, through an integrated discovery and targeted proteomic approach, this study serves as the first report to detect and confirm novel retinal protein changes and significant biological functions in the early LIM mammalian guinea pigs. The study provides new workflow and insights for further research to myopia control.<\/jats:p>","DOI":"10.3390\/ijms22094721","type":"journal-article","created":{"date-parts":[[2021,4,29]],"date-time":"2021-04-29T10:30:41Z","timestamp":1619692241000},"page":"4721","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["SWATH Based Quantitative Proteomics Reveals Significant Lipid Metabolism in Early Myopic Guinea Pig Retina"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0464-1705","authenticated-orcid":false,"given":"Jingfang","family":"Bian","sequence":"first","affiliation":[{"name":"Centre for Myopia Research, School of Optometry, The Hong Kong Polytechnic University, Kowloon, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying-Hon","family":"Sze","sequence":"additional","affiliation":[{"name":"Centre for Myopia Research, School of Optometry, The Hong Kong Polytechnic University, Kowloon, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7561-9121","authenticated-orcid":false,"given":"Dennis Yan-Yin","family":"Tse","sequence":"additional","affiliation":[{"name":"Centre for Myopia Research, School of Optometry, The Hong Kong Polytechnic University, Kowloon, Hong Kong, China"},{"name":"Centre for Eye and Vision Research (CEVR), 17W Hong Kong Science Park, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1938-8397","authenticated-orcid":false,"given":"Chi-Ho","family":"To","sequence":"additional","affiliation":[{"name":"Centre for Myopia Research, School of Optometry, The Hong Kong Polytechnic University, Kowloon, Hong Kong, China"},{"name":"Centre for Eye and Vision Research (CEVR), 17W Hong Kong Science Park, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6761-1592","authenticated-orcid":false,"given":"Sally A.","family":"McFadden","sequence":"additional","affiliation":[{"name":"School of Psychology, College of Engineering, Science and the Environment, University of Newcastle, Callaghan, NSW 2308, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6808-5018","authenticated-orcid":false,"given":"Carly Siu-Yin","family":"Lam","sequence":"additional","affiliation":[{"name":"Centre for Myopia Research, School of Optometry, The Hong Kong Polytechnic University, Kowloon, Hong Kong, China"},{"name":"Centre for Eye and Vision Research (CEVR), 17W Hong Kong Science Park, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"King-Kit","family":"Li","sequence":"additional","affiliation":[{"name":"Centre for Myopia Research, School of Optometry, The Hong Kong Polytechnic University, Kowloon, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3511-5620","authenticated-orcid":false,"given":"Thomas Chuen","family":"Lam","sequence":"additional","affiliation":[{"name":"Centre for Myopia Research, School of Optometry, The Hong Kong Polytechnic University, Kowloon, Hong Kong, China"},{"name":"Centre for Eye and Vision Research (CEVR), 17W Hong Kong Science Park, Hong Kong, China"},{"name":"Shenzhen Research Institute, The Hong Kong Polytechnic University, Shenzhen 518052, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e339","DOI":"10.1016\/S2214-109X(13)70113-X","article-title":"Causes of vision loss worldwide, 1990\u20132010: A systematic analysis","volume":"1","author":"Bourne","year":"2013","journal-title":"Lancet Glob. Health"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1038\/519276a","article-title":"The myopia boom","volume":"519","author":"Dolgin","year":"2015","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Curtin, B.J. (1985). The Myopias: Basic Science and Clinical Management, Harper and Row.","DOI":"10.1097\/00006982-198600620-00013"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1080\/09286580701331974","article-title":"The epidemiology of age-related eye diseases in Mainland China","volume":"14","author":"Zhou","year":"2007","journal-title":"Ophthalmic Epidemiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1136\/bjo.2005.083733","article-title":"The epidemiology of age related eye diseases in Asia","volume":"90","author":"Wong","year":"2006","journal-title":"Br. J. Ophthalmol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1001\/archopht.1991.01080020090051","article-title":"The Lens Opacities Case-Control Study\u2014Risk-Factors for Cataract","volume":"109","author":"Leske","year":"1991","journal-title":"Arch. Ophthalmol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1080\/02713683.2016.1223317","article-title":"Correlations Between MMPs and TIMPs Levels in Aqueous Humor from High Myopia and Cataract Patients","volume":"42","author":"Jia","year":"2017","journal-title":"Curr. Eye Res."},{"key":"ref_8","first-page":"750","article-title":"High myopia as a risk factor in primary open angle glaucoma","volume":"5","author":"Chen","year":"2012","journal-title":"Int. J. Ophthalmol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1159\/000310760","article-title":"Severe myopia as a risk factor for progressive visual field loss in primary open-angle glaucoma","volume":"211","author":"Chihara","year":"1997","journal-title":"Ophthalmologica"},{"key":"ref_10","first-page":"141","article-title":"Bilateral retinal detachment and high myopia: Report of nine cases","volume":"38","author":"Mahfoudi","year":"2015","journal-title":"J. Fr. D Ophtalmol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1016\/S0886-3350(97)80087-9","article-title":"Pseudophakic retinal detachment in high axial myopia","volume":"23","author":"Jacobi","year":"1997","journal-title":"J. Cataract Refract. Surg."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1126\/science.694514","article-title":"Extreme myopia produced by modest change in early visual experience","volume":"201","author":"Wallman","year":"1978","journal-title":"Science"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.neuron.2004.08.008","article-title":"Homeostasis of eye growth and the question of myopia","volume":"43","author":"Wallman","year":"2004","journal-title":"Neuron"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1167\/iovs.09-4153","article-title":"Mouse experimental myopia has features of primate myopia","volume":"51","author":"Tkatchenko","year":"2010","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1016\/j.visres.2008.01.004","article-title":"Two models of experimental myopia in the mouse","volume":"48","author":"Barathi","year":"2008","journal-title":"Vis. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1167\/iovs.11-8354","article-title":"Alterations in protein expression in tree shrew sclera during development of lens-induced myopia and recovery","volume":"53","author":"Frost","year":"2012","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3505","DOI":"10.1016\/S0042-6989(98)00053-4","article-title":"The susceptible period for deprivation-induced myopia in tree shrew","volume":"38","author":"Siegwart","year":"1998","journal-title":"Vis. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/0006-8993(77)90872-1","article-title":"Myopia in the lid-sutured tree shrew (Tupaia glis)","volume":"124","author":"Sherman","year":"1977","journal-title":"Brain Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1016\/j.visres.2006.12.019","article-title":"Emmetropization and schematic eye models in developing pigmented guinea pigs","volume":"47","author":"Howlett","year":"2007","journal-title":"Vis. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.visres.2008.10.008","article-title":"Spectacle lens compensation in the pigmented guinea pig","volume":"49","author":"Howlett","year":"2009","journal-title":"Vis. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1167\/iovs.08-2463","article-title":"Spontaneous axial myopia and emmetropization in a strain of wild-type guinea pig (Cavia porcellus)","volume":"50","author":"Jiang","year":"2009","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4681","DOI":"10.1073\/pnas.0600589103","article-title":"Form deprivation modulates retinal neurogenesis in primate experimental myopia","volume":"103","author":"Tkatchenko","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1097\/00006324-198107000-00008","article-title":"Primate myopia","volume":"58","author":"Young","year":"1981","journal-title":"Am. J. Optom. Physiol. Opt."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1038\/nm0895-761","article-title":"Spectacle lenses alter eye growth and the refractive status of young monkeys","volume":"1","author":"Hung","year":"1995","journal-title":"Nat. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1097\/00006324-199906000-00023","article-title":"Form deprivation myopia in adolescent monkeys","volume":"76","author":"Smith","year":"1999","journal-title":"Optom. Vis. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1016\/j.visres.2003.11.002","article-title":"Retinoic acid signals the direction of ocular elongation in the guinea pig eye","volume":"44","author":"McFadden","year":"2004","journal-title":"Vis. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.visres.2005.06.036","article-title":"Form-deprivation myopia in the guinea pig (Cavia porcellus)","volume":"46","author":"Howlett","year":"2006","journal-title":"Vis. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.exer.2004.08.003","article-title":"Immunocytochemical development of the guinea pig retina","volume":"80","author":"Loeliger","year":"2005","journal-title":"Exp. Eye Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"M31","DOI":"10.1167\/iovs.18-25967","article-title":"IMI\u2014Report on Experimental Models of Emmetropization and Myopia","volume":"60","author":"Troilo","year":"2019","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1016\/0042-6989(94)00233-C","article-title":"Choroidal and scleral mechanisms of compensation for spectacle lenses in chicks","volume":"35","author":"Wildsoet","year":"1995","journal-title":"Vis. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"993","DOI":"10.3109\/02713688709034870","article-title":"Visual deprivation causes myopia in chicks with optic nerve section","volume":"6","author":"Troilo","year":"1987","journal-title":"Curr. Eye Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3559","DOI":"10.7150\/thno.20797","article-title":"Mass spectrometry-assisted gel-based proteomics in cancer biomarker discovery: Approaches and application","volume":"7","author":"Huang","year":"2017","journal-title":"Theranostics"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1007\/978-1-62703-556-9_17","article-title":"Gel electrophoresis-based proteomics of senescent tissues","volume":"1048","author":"Carberry","year":"2013","journal-title":"Methods Mol. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2343","DOI":"10.1021\/cr3003533","article-title":"Protein analysis by shotgun\/bottom-up proteomics","volume":"113","author":"Zhang","year":"2013","journal-title":"Chem. Rev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"5683","DOI":"10.1021\/ac010617e","article-title":"An automated multidimensional protein identification technology for shotgun proteomics","volume":"73","author":"Wolters","year":"2001","journal-title":"Anal. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1146\/annurev.biophys.33.111502.082538","article-title":"Mass spectral analysis in proteomics","volume":"33","author":"Yates","year":"2004","journal-title":"Annu. Rev. Biophys. Biomol. Struct."},{"key":"ref_37","first-page":"494572","article-title":"Gel-based and gel-free quantitative proteomics approaches at a glance","volume":"2012","author":"Abdallah","year":"2012","journal-title":"Int. J. Plant Genom."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1021\/pr050280n","article-title":"A chick retinal proteome database and differential retinal protein expressions during early ocular development","volume":"5","author":"Lam","year":"2006","journal-title":"J. Proteome Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4135","DOI":"10.1021\/pr0701097","article-title":"Application of fluorescence difference gel electrophoresis technology in searching for protein biomarkers in chick myopia","volume":"6","author":"Lam","year":"2007","journal-title":"J. Proteome Res."},{"key":"ref_40","first-page":"5571","article-title":"Early quantitative profiling of differential retinal protein expression in lens-induced myopia in guinea pig using fluorescence difference two-dimensional gel electrophoresis","volume":"17","author":"Wu","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"37","DOI":"10.2174\/1570164610666140109002531","article-title":"Differential Retinal Protein Expressions During form Deprivation Myopia in Albino Guinea Pigs","volume":"11","author":"Wu","year":"2014","journal-title":"Curr. Proteom."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1038\/s41467-017-00249-5","article-title":"Multi-laboratory assessment of reproducibility, qualitative and quantitative performance of SWATH-mass spectrometry","volume":"8","author":"Collins","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1074\/mcp.M113.035550","article-title":"Reproducible and consistent quantification of the Saccharomyces cerevisiae proteome by SWATH-mass spectrometry","volume":"14","author":"Selevsek","year":"2015","journal-title":"Mol. Cell. Proteom."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Gillet, L.C., Navarro, P., Tate, S., Rost, H., Selevsek, N., Reiter, L., Bonner, R., and Aebersold, R. (2012). Targeted data extraction of the MS\/MS spectra generated by data-independent acquisition: A new concept for consistent and accurate proteome analysis. Mol. Cell. Proteom., 11.","DOI":"10.1074\/mcp.O111.016717"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jprot.2018.03.023","article-title":"Integrated SWATH-based and targeted-based proteomics provide insights into the retinal emmetropization process in guinea pig","volume":"181","author":"Shan","year":"2018","journal-title":"J. Proteom."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1167\/tvst.9.3.16","article-title":"Comparison of Capillary and Schirmer Strip Tear Fluid Sampling Methods Using SWATH-MS Proteomics Approach","volume":"9","author":"Aapola","year":"2020","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3753","DOI":"10.1021\/acs.jproteome.7b00449","article-title":"New Insight of Common Regulatory Pathways in Human Trabecular Meshwork Cells in Response to Dexamethasone and Prednisolone Using an Integrated Quantitative Proteomics: SWATH and MRM-HR Mass Spectrometry","volume":"16","author":"Shan","year":"2017","journal-title":"J. Proteome Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3294","DOI":"10.1167\/iovs.18-23831","article-title":"SWATH-MS Proteomic Analysis of Oxygen-Induced Retinopathy Reveals Novel Potential Therapeutic Targets","volume":"59","author":"Vahatupa","year":"2018","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1038\/nmeth.2015","article-title":"Selected reaction monitoring-based proteomics: Workflows, potential, pitfalls and future directions","volume":"9","author":"Picotti","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1038\/nbt1235","article-title":"Protein biomarker discovery and validation: The long and uncertain path to clinical utility","volume":"24","author":"Rifai","year":"2006","journal-title":"Nat. Biotechnol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.1002\/jms.1412","article-title":"Rapid screening and characterization of drug metabolites using a multiple ion monitoring-dependent MS\/MS acquisition method on a hybrid triple quadrupole-linear ion trap mass spectrometer","volume":"43","author":"Yao","year":"2008","journal-title":"J. Mass Spectrom."},{"key":"ref_52","first-page":"1229","article-title":"Multiple reaction monitoring for quantitative biomarker analysis in proteomics and metabolomics","volume":"877","author":"Kitteringham","year":"2009","journal-title":"J. Chromatogr."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e8644","DOI":"10.1002\/rcm.8644","article-title":"A sensitive and cost-effective high-performance liquid chromatography\/tandem mass spectrometry (multiple reaction monitoring) method for the clinical measurement of serum hepcidin","volume":"34","author":"Chen","year":"2020","journal-title":"Rapid Commun. Mass Spectrom."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1074\/mcp.M116.064758","article-title":"Development of a Multiplexed Liquid Chromatography Multiple-Reaction-Monitoring Mass Spectrometry (LC-MRM\/MS) Method for Evaluation of Salivary Proteins as Oral Cancer Biomarkers","volume":"16","author":"Chen","year":"2017","journal-title":"Mol. Cell. Proteom."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"D362","DOI":"10.1093\/nar\/gkw937","article-title":"The STRING database in 2017: Quality-controlled protein-protein association networks, made broadly accessible","volume":"45","author":"Szklarczyk","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1002\/pmic.201700052","article-title":"Comparison of fractionation proteomics for local SWATH library building","volume":"17","author":"Govaert","year":"2017","journal-title":"Proteomics"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"D442","DOI":"10.1093\/nar\/gky1106","article-title":"The PRIDE database and related tools and resources in 2019: Improving support for quantification data","volume":"47","author":"Csordas","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1002\/pmic.201500242","article-title":"Proteome and pathway effects of chronic haloperidol treatment in mouse hippocampus","volume":"16","author":"Schubert","year":"2016","journal-title":"Proteomics"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1002\/oby.21482","article-title":"Proinflammatory and lipid biomarkers mediate metabolically healthy obesity: A proteomics study","volume":"24","author":"Doumatey","year":"2016","journal-title":"Obesity"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12920-019-0560-1","article-title":"Analysis of genetic networks regulating refractive eye development in collaborative cross progenitor strain mice reveals new genes and pathways underlying human myopia","volume":"12","author":"Tkatchenko","year":"2019","journal-title":"BMC Med Genom."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Tkatchenko, T.V., Troilo, D., Benavente-Perez, A., and Tkatchenko, A.V. (2018). Gene expression in response to optical defocus of opposite signs reveals bidirectional mechanism of visually guided eye growth. PLoS Biol., 16.","DOI":"10.1371\/journal.pbio.2006021"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Giummarra, L., Crewther, S.G., Riddell, N., Murphy, M.J., and Crewther, D.P. (2018). Pathway analysis identifies altered mitochondrial metabolism, neurotransmission, structural pathways and complement cascade in retina\/RPE\/choroid in chick model of form-deprivation myopia. Peerj, 6.","DOI":"10.7717\/peerj.5048"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"9719","DOI":"10.1038\/s41598-017-10277-2","article-title":"Novel evidence for complement system activation in chick myopia and hyperopia models: A meta-analysis of transcriptome datasets","volume":"7","author":"Riddell","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_64","unstructured":"Zhang, Y., Liu, Y., Xu, J., Nimri, N., and Wildsoet, C.F. (2010). Microarray Analysis of RPE Gene Expression in Chicks During Long-term Imposed Myopic Defocus. Investig. Ophthalmol. Vis. Sci., 51."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1167\/iovs.05-0195","article-title":"Melatonin receptors in chick ocular tissues: Implications for a role of melatonin in ocular growth regulation","volume":"47","author":"Rada","year":"2006","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1167\/iovs.16-21278","article-title":"Gene Expression and Pathways Underlying Form Deprivation Myopia in the Guinea Pig Sclera","volume":"59","author":"Srinivasalu","year":"2018","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"E7091","DOI":"10.1073\/pnas.1721443115","article-title":"Scleral hypoxia is a target for myopia control","volume":"115","author":"Wu","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_68","first-page":"1859","article-title":"mTor signaling is required for the formation of proliferating Muller glia-derived progenitor cells in the chick retina","volume":"143","author":"Zelinka","year":"2016","journal-title":"Development"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Yang, J., Zhou, S., Gu, J., Guo, M., Xia, H., and Liu, Y. (2015). UPR Activation and the Down-Regulation of \u03b1-Crystallin in Human High Myopia-Related Cataract Lens Epithelium. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0137582"},{"key":"ref_70","first-page":"131","article-title":"Expressions of cellular retinoic acid binding proteins I and retinoic acid receptor-beta in the guinea pig eyes with experimental myopia","volume":"4","author":"Huang","year":"2011","journal-title":"Int. J. Ophthalmol."},{"key":"ref_71","first-page":"1795","article-title":"All-trans retinoic acid modulates mitogen-activated protein kinase pathway activation in human scleral fibroblasts through retinoic acid receptor beta","volume":"19","author":"Huo","year":"2013","journal-title":"Mol. Vis."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Li, H., Cui, D., Zhao, F., Huo, L., Hu, J., and Zeng, J. (2015). BMP-2 Is Involved in Scleral Remodeling in Myopia Development. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0125219"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2671","DOI":"10.3892\/mmr.2016.4843","article-title":"Retinal and choroidal expression of BMP-2 in lens-induced myopia and recovery from myopia in guinea pigs","volume":"13","author":"Li","year":"2016","journal-title":"Mol. Med. Rep."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.exer.2013.02.007","article-title":"An updated view on the role of dopamine in myopia","volume":"114","author":"Feldkaemper","year":"2013","journal-title":"Exp. Eye Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2306","DOI":"10.1167\/iovs.16-20402","article-title":"Bright Light Suppresses Form-Deprivation Myopia Development With Activation of Dopamine D1 Receptor Signaling in the ON Pathway in Retina","volume":"58","author":"Chen","year":"2017","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.preteyeres.2017.06.003","article-title":"Dopamine signaling and myopia development: What are the key challenges","volume":"61","author":"Zhou","year":"2017","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.exer.2014.04.005","article-title":"Gene expression signatures in tree shrew choroid during lens-induced myopia and recovery","volume":"123","author":"He","year":"2014","journal-title":"Exp. Eye Res."},{"key":"ref_78","first-page":"1436","article-title":"Insulin, insulin-like growth factor-1, insulin receptor, and insulin-like growth factor-1 receptor expression in the chick eye and their regulation with imposed myopic or hyperopic defocus","volume":"17","author":"Penha","year":"2011","journal-title":"Mol. Vis."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.exer.2012.03.019","article-title":"The combination of IGF1 and FGF2 and the induction of excessive ocular growth and extreme myopia","volume":"99","author":"Ritchey","year":"2012","journal-title":"Exp. Eye. Res."},{"key":"ref_80","first-page":"54","article-title":"Expressions of type I collagen, alpha 2 integrin and beta 1 integrin in sclera of guinea pig with defocus myopia and inhibitory effects of bFGF on the formation of myopia","volume":"6","author":"Tian","year":"2013","journal-title":"Int. J. Ophthalmol."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Tao, Y.J., Pan, M.Z., Liu, S.F., Fang, F., Lu, R.X., Lu, C.Y., Zheng, M., An, J.H., Xu, H.J., and Zhao, F.X. (2013). cAMP Level Modulates Scleral Collagen Remodeling, a Critical Step in the Development of Myopia. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0071441"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"8151","DOI":"10.1167\/iovs.14-14233","article-title":"Cyclic Adenosine Monophosphate Activates Retinal Apolipoprotein A1 Expression and Inhibits Myopic Eye Growth","volume":"56","author":"Chun","year":"2015","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1167\/iovs.13-11724","article-title":"Integration of defocus by dual power Fresnel lenses inhibits myopia in the mammalian eye","volume":"55","author":"McFadden","year":"2014","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"4846","DOI":"10.1167\/iovs.07-0101","article-title":"Variation of the contribution from axial length and other oculometric parameters to refraction by age and ethnicity","volume":"48","author":"Ip","year":"2007","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.4103\/njcp.njcp_183_16","article-title":"Axial length\/corneal radius of curvature ratio and refractive status in an adult Nigerian population","volume":"20","author":"Badmus","year":"2017","journal-title":"Niger. J. Clin. Pract."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1750","DOI":"10.1016\/j.dib.2018.08.119","article-title":"Data on differentially expressed proteins in retinal emmetropization process in guinea pig using integrated SWATH-based and targeted-based proteomics","volume":"21","author":"Shan","year":"2018","journal-title":"Data Brief"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Velez, G., Machlab, D.A., Tang, P.H., Sun, Y., Tsang, S.H., Bassuk, A.G., and Mahajan, V.B. (2018). Proteomic analysis of the human retina reveals region-specific susceptibilities to metabolic- and oxidative stress-related diseases. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0193250"},{"key":"ref_88","unstructured":"Yu, F. (2016). Proteome Profiling and Relative Quantification of Protein Expressions in the Chick Vitreous and Retina During Compensated Ocular Growth, The Hong Kong Polytechnic University."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"12649","DOI":"10.1038\/s41598-017-12650-7","article-title":"Isotope-coded protein label based quantitative proteomic analysis reveals significant up-regulation of apolipoprotein A1 and ovotransferrin in the myopic chick vitreous","volume":"7","author":"Yu","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/S1350-9462(00)00014-8","article-title":"Vertebrate photoreceptors","volume":"20","author":"Ebrey","year":"2001","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_91","first-page":"2068","article-title":"Retinal degeneration increases susceptibility to myopia in mice","volume":"19","author":"Park","year":"2013","journal-title":"Mol. Vis."},{"key":"ref_92","first-page":"1496","article-title":"A screen for mutations in the transducin gene GNB1 in patients with autosomal dominant retinitis pigmentosa","volume":"12","author":"Mylvaganam","year":"2006","journal-title":"Mol. Vis."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1073\/pnas.86.2.704","article-title":"Retinal dopamine and form-deprivation myopia","volume":"86","author":"Stone","year":"1989","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1097\/00006324-200402000-00012","article-title":"Inhibitory effects of apomorphine and atropine and their combination on myopia in chicks","volume":"81","author":"Schmid","year":"2004","journal-title":"Optom. Vis. Sci."},{"key":"ref_95","first-page":"2824","article-title":"Inhibition of experimental myopia by a dopamine agonist: Different effectiveness between form deprivation and hyperopic defocus in guinea pigs","volume":"17","author":"Dong","year":"2011","journal-title":"Mol. Vis."},{"key":"ref_96","first-page":"1674","article-title":"Effects of Apomorphine, a Dopamine Receptor Agonist, on Ocular Refraction and Axial Elongation in a Primate Model of Myopia","volume":"32","author":"Iuvone","year":"1991","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2475","DOI":"10.1167\/iovs.13-12361","article-title":"Daily Injection But Not Continuous Infusion of Apomorphine Inhibits Form-Deprivation Myopia in Mice","volume":"56","author":"Yan","year":"2015","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Jimenez, G. (2017). How Genetics Has Helped Piece Together the MAPK Signaling Pathway. ERK Signaling: Methods and Protocols, Springer.","DOI":"10.1007\/978-1-4939-6424-6"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1586\/17469899.2016.1164597","article-title":"GWAS in myopia: Insights into disease and implications for the clinic","volume":"11","author":"Williams","year":"2016","journal-title":"Expert Rev. Ophthalmol."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Beuerman, R.W., Goh, L.K., and Barathi, V.A. (2010). Gene Analysis in Experimental Animal Models of Myopia. Myopia, World Scientific.","DOI":"10.1142\/9789812832986"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1002\/pmic.201400270","article-title":"SWATH enables precise label-free quantification on proteome scale","volume":"15","author":"Huang","year":"2015","journal-title":"Proteomics"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2135","DOI":"10.1039\/C5MB00234F","article-title":"In-depth comparative proteomic analysis of yeast proteome using iTRAQ and SWATH based MS","volume":"11","author":"Basak","year":"2015","journal-title":"Mol. Biosyst."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/0014-4835(89)90088-2","article-title":"Lipid peroxidation and human cataractogenesis in diabetes and severe myopia","volume":"49","author":"Simonelli","year":"1989","journal-title":"Exp. Eye Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"750637","DOI":"10.1155\/2015\/750637","article-title":"Oxidative stress in myopia","volume":"2015","author":"Francisco","year":"2015","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"2777","DOI":"10.1038\/s41598-017-03075-3","article-title":"Changes in retinal metabolic profiles associated with form deprivation myopia development in guinea pigs","volume":"7","author":"Yang","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.4155\/bio.12.126","article-title":"The use of selected reaction monitoring in quantitative proteomics","volume":"4","author":"Holman","year":"2012","journal-title":"Bioanalysis"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1007\/978-1-60761-780-8_9","article-title":"Selected reaction monitoring applied to quantitative proteomics","volume":"658","author":"Kiyonami","year":"2010","journal-title":"Methods Mol. Biol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"11507","DOI":"10.1096\/fj.201900914RR","article-title":"Biallelic mutation of human SLC6A6 encoding the taurine transporter TAUT is linked to early retinal degeneration","volume":"33","author":"Preising","year":"2019","journal-title":"FASEB J."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.tips.2006.05.003","article-title":"Neurotransmitter transporters: Molecular function of important drug targets","volume":"27","author":"Gether","year":"2006","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"2138","DOI":"10.1016\/j.bbamem.2008.04.012","article-title":"Function of taurine transporter (Slc6a6\/TauT) as a GABA transporting protein and its relevance to GABA transport in rat retinal capillary endothelial cells","volume":"1778","author":"Tomi","year":"2008","journal-title":"Biochim. Biophys. Acta-Biomembr."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.neuroscience.2014.12.022","article-title":"Effects of Electroacupuncture on the Levels of Retinal Gamma-Aminobutyric Acid and Its Receptors in a Guinea Pig Model of Lens-Induced Myopia","volume":"287","author":"Sha","year":"2015","journal-title":"Neuroscience"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.brainresbull.2017.01.017","article-title":"GABA and GABA receptors alterations in the primary visual cortex of concave lens-induced myopic model","volume":"130","author":"Zhao","year":"2017","journal-title":"Brain Res. Bull."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"108","DOI":"10.3109\/13816810.2016.1164193","article-title":"Prostaglandins in the eye: Function, expression, and roles in glaucoma","volume":"38","author":"Doucette","year":"2017","journal-title":"Ophthalmic Genet."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/S2589-3777(19)30053-9","article-title":"Hub Genes of Astrocyte Involved in Glaucoma with Ocular Hypertension by Integrated Bioinformatics Analysis","volume":"1","author":"Yang","year":"2018","journal-title":"Digit. Chin. Med."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"107740","DOI":"10.1016\/j.exer.2019.107740","article-title":"Effect of chronic topical latanoprost on the sclera and lamina cribrosa of form-deprived myopic Guinea pigs","volume":"186","author":"Yao","year":"2019","journal-title":"Exp. Eye Res."},{"key":"ref_116","first-page":"163","article-title":"The transport of copper","volume":"380","author":"Harris","year":"1993","journal-title":"Prog. Clin. Biol. Res."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1172\/JCI118768","article-title":"Ceruloplasmin gene expression in the murine central nervous system","volume":"98","author":"Klomp","year":"1996","journal-title":"J. Clin. Investig."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1167\/iovs.06-0497","article-title":"Ceruloplasmin upregulation in retina of murine and human glaucomatous eyes","volume":"48","author":"Stasi","year":"2007","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s12011-016-0805-1","article-title":"Serum Concentration of Zinc, Copper, Selenium, Manganese, and Cu\/Zn Ratio in Children and Adolescents with Myopia","volume":"176","author":"Fedor","year":"2017","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1182\/blood-2012-02-408328","article-title":"CDP-diacylglycerol synthetase-controlled phosphoinositide availability limits VEGFA signaling and vascular morphogenesis","volume":"120","author":"Pan","year":"2012","journal-title":"Blood"},{"key":"ref_121","first-page":"955","article-title":"Changes in gene expression associated with retinal degeneration in the rd3 mouse","volume":"19","author":"Cheng","year":"2013","journal-title":"Mol. Vis."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.exer.2014.07.022","article-title":"Effects of a human VEGF antibody (Bevacizumab) on deprivation myopia and choroidal thickness in the chicken","volume":"127","author":"Mathis","year":"2014","journal-title":"Exp. Eye Res."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1080\/13816810.2016.1247459","article-title":"Ocular manifestations in the X-linked intellectual disability syndromes","volume":"38","author":"Couser","year":"2017","journal-title":"Ophthalmic Genet."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"2244","DOI":"10.1172\/JCI66466","article-title":"CCDC22 deficiency in humans blunts activation of proinflammatory NF-kappaB signaling","volume":"123","author":"Starokadomskyy","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_125","first-page":"150","article-title":"The expression of cytokines in aqueous humor of high myopic patients with cataracts","volume":"26","author":"Zhang","year":"2020","journal-title":"Mol. Vis."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"481","DOI":"10.3892\/mmr.2013.1808","article-title":"Early-onset severe hereditary sensory and autonomic neuropathy type 1 with S331F SPTLC1 mutation","volume":"9","author":"Suh","year":"2014","journal-title":"Mol. Med. Rep."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"338","DOI":"10.7326\/0003-4819-138-4-200302180-00014","article-title":"Fabry disease, an under-recognized multisystemic disorder: Expert recommendations for diagnosis, management, and enzyme replacement therapy","volume":"138","author":"Desnick","year":"2003","journal-title":"Ann. Intern. Med."},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Pitz, S., Kalkum, G., Arash, L., Karabul, N., Sodi, A., Larroque, S., Beck, M., and Gal, A. (2015). Ocular signs correlate well with disease severity and genotype in Fabry disease. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0120814"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1111\/aos.12588","article-title":"Ophthalmic experience over 10 years in an observational nationwide Danish cohort of Fabry patients with access to enzyme replacement","volume":"93","author":"Fledelius","year":"2015","journal-title":"Acta Ophthalmol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1038\/nature10530","article-title":"A high-resolution map of human evolutionary constraint using 29 mammals","volume":"478","author":"Garber","year":"2011","journal-title":"Nature"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"5911","DOI":"10.1167\/iovs.13-11708","article-title":"Egr-1 mRNA Expression Is a Marker for the Direction of Mammalian Ocular Growth","volume":"55","author":"Ashby","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"4359","DOI":"10.1021\/acs.jproteome.5b00543","article-title":"The Use of Variable Q1 Isolation Windows Improves Selectivity in LC-SWATH-MS Acquisition","volume":"14","author":"Zhang","year":"2015","journal-title":"J. Proteome Res."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"bar009","DOI":"10.1093\/database\/bar009","article-title":"UniProt Knowledgebase: A hub of integrated protein data","volume":"2011","author":"Magrane","year":"2011","journal-title":"Database"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1038\/nprot.2013.092","article-title":"Large-scale gene function analysis with the PANTHER classification system","volume":"8","author":"Mi","year":"2013","journal-title":"Nat. Protoc."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"3442","DOI":"10.1093\/nar\/28.18.3442","article-title":"STRING: A web-server to retrieve and display the repeatedly occurring neighbourhood of a gene","volume":"28","author":"Snel","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1093\/bioinformatics\/btt703","article-title":"Causal analysis approaches in Ingenuity Pathway Analysis","volume":"30","author":"Kramer","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"S50","DOI":"10.1016\/j.cbpa.2008.04.619","article-title":"Ingenuity Pathways Analysis: Software for discovering and modelling pathways and networks in your systems data","volume":"150","author":"Guerra","year":"2008","journal-title":"Comp. Biochem. Physiol. Mol. Integr. Physiol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1038\/nbt.1905","article-title":"Selected reaction monitoring mass spectrometry reveals the dynamics of signaling through the GRB2 adaptor","volume":"29","author":"Bisson","year":"2011","journal-title":"Nat. Biotechnol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/9\/4721\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:55:26Z","timestamp":1760162126000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/9\/4721"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,29]]},"references-count":138,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2021,5]]}},"alternative-id":["ijms22094721"],"URL":"https:\/\/doi.org\/10.3390\/ijms22094721","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,29]]}}}