{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T22:16:55Z","timestamp":1793225815581,"version":"4.5.0"},"reference-count":56,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T00:00:00Z","timestamp":1787356800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T00:00:00Z","timestamp":1787356800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Funct Integr Genomics"],"published-print":{"date-parts":[[2026,12]]},"DOI":"10.1007\/s10142-026-02013-9","type":"journal-article","created":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T01:09:21Z","timestamp":1787360961000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Dynamics-aware evolutionary profiling uncouples structural rigidity from functional motion to enable enhanced variant interpretation"],"prefix":"10.1007","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-1011-7661","authenticated-orcid":false,"given":"Taner","family":"Karag\u00f6l","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7864-0732","authenticated-orcid":false,"given":"Alper","family":"Karag\u00f6l","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,22]]},"reference":[{"issue":"4","key":"2013_CR1","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1002\/wics.101","volume":"2","author":"H Abdi","year":"2010","unstructured":"Abdi H, Williams LJ (2010) Principal component analysis. Wiley interdisciplinary reviews: Comput Stat 2(4):433\u2013459","journal-title":"Wiley interdisciplinary reviews: Comput Stat"},{"issue":"8016","key":"2013_CR2","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1038\/s41586-024-07487-w","volume":"630","author":"J Abramson","year":"2024","unstructured":"Abramson J, Adler J, Dunger J, Evans R, Green T, Pritzel A, Jumper JM (2024) Accurate structure prediction of biomolecular interactions with AlphaFold 3. Nature 630(8016):493\u2013500","journal-title":"Nature"},{"key":"2013_CR3","doi-asserted-by":"crossref","unstructured":"Karag\u00f6l A, Karag\u00f6l T (2024) An Evolutionary Statistics Toolkit for Simplified Sequence Analysis on Web with Client-Side Processing. bioRxiv, 2024\u20132008","DOI":"10.1101\/2024.08.01.606148"},{"key":"2013_CR4","doi-asserted-by":"crossref","unstructured":"Berman, H. M., Westbrook, J., Feng, Z., Gilliland, G., Bhat, T. N., Weissig, H., Bourne, P. E. (2000). The protein data bank. Nucleic acids research, 28(1), 235\u2013242.","DOI":"10.1093\/nar\/28.1.235"},{"issue":"6664","key":"2013_CR5","doi-asserted-by":"publisher","DOI":"10.1126\/science.adg7492","volume":"381","author":"J Cheng","year":"2023","unstructured":"Cheng J, Novati G, Pan J, Bycroft C, \u017demgulyt\u0117 A, Applebaum T, Avsec \u017d (2023) Accurate proteome-wide missense variant effect prediction with AlphaMissense. Science 381(6664):eadg7492","journal-title":"Science"},{"key":"2013_CR6","doi-asserted-by":"crossref","unstructured":"Karag\u00f6l T, Karag\u00f6l A, Zhang S (2025) Co-evolution of alpha-helical transmembrane protein residues: large-scale variant profiling and complete mutational landscape of 2277 known PDB entries representing 504 unique human protein sequences. J Mol Evol, 1\u201319","DOI":"10.1007\/s00239-025-10262-8"},{"issue":"3","key":"2013_CR7","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1080\/00401706.1964.10490181","volume":"6","author":"OJ Dunn","year":"1964","unstructured":"Dunn OJ (1964) Multiple comparisons using rank sums. Technometrics 6(3):241\u2013252","journal-title":"Technometrics"},{"issue":"53","key":"2013_CR8","doi-asserted-by":"publisher","first-page":"44289","DOI":"10.1074\/jbc.M112.394866","volume":"287","author":"D Gagn\u00e9","year":"2012","unstructured":"Gagn\u00e9 D, Charest LA, Morin S, Kovrigin EL, Doucet N (2012) Conservation of flexible residue clusters among structural and functional enzyme homologues. J Biol Chem 287(53):44289\u201344300","journal-title":"J Biol Chem"},{"issue":"1","key":"2013_CR9","doi-asserted-by":"publisher","first-page":"4378","DOI":"10.1038\/s41467-019-12365-5","volume":"10","author":"JC Heiby","year":"2019","unstructured":"Heiby JC, Goretzki B, Johnson CM, Hellmich UA, Neuweiler H (2019) Methionine in a protein hydrophobic core drives tight interactions required for assembly of spider silk. Nat Commun 10(1):4378","journal-title":"Nat Commun"},{"key":"2013_CR10","doi-asserted-by":"crossref","unstructured":"H\u00f6gel, P., G\u00f6tz, A., Kuhne, F., Ebert, M., Stelzer, W., Rand, K. D., \u2026 Langosch, D.(2018). Glycine perturbs local and global conformational flexibility of a transmembrane helix.Biochemistry, 57(8), 1326\u20131337","DOI":"10.1021\/acs.biochem.7b01197"},{"key":"2013_CR11","doi-asserted-by":"crossref","unstructured":"Hopf, T. A., Green, A. G., Schubert, B., Mersmann, S., Sch\u00e4rfe, C. P., Ingraham, J.B., Marks, D. S. (2019). The EVcouplings Python framework for coevolutionary sequence analysis.Bioinformatics, 35(9), 1582\u20131584","DOI":"10.1093\/bioinformatics\/bty862"},{"key":"2013_CR12","doi-asserted-by":"crossref","unstructured":"Karag\u00f6l A, Karag\u00f6l T (2026) In Silico Directed Evolution of Humanized Peptide Transporters via Attention-Guided Epistatic Rescue. 2026","DOI":"10.21203\/rs.3.rs-9198655\/v1"},{"key":"2013_CR13","doi-asserted-by":"crossref","unstructured":"Karag\u00f6l T, Karag\u00f6l A, Zhang S (2026) Integrative Structural Bioinformatics and Molecular Dynamics Analyses of Synaptic Vesicle Proteins and Their Water-Soluble QTY-Variants Reveal Membrane Constraints and Evolutionary Coupling of T\u21d4V. J Mol Evol, 1\u201322","DOI":"10.1007\/s00239-026-10315-6"},{"key":"2013_CR14","doi-asserted-by":"crossref","unstructured":"Metwally A, Agrawal D, Abbadi E (2005), January A. Efficient computation of frequent and top-k elements in data streams. In International conference on database theory (pp. 398\u2013412). Berlin, Heidelberg: Springer Berlin Heidelberg","DOI":"10.1007\/978-3-540-30570-5_27"},{"issue":"1","key":"2013_CR15","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1186\/1471-2105-11-431","volume":"11","author":"LS Johnson","year":"2010","unstructured":"Johnson LS, Eddy SR, Portugaly E (2010) Hidden Markov model speed heuristic and iterative HMM search procedure. BMC Bioinformatics 11(1):431","journal-title":"BMC Bioinformatics"},{"key":"2013_CR16","doi-asserted-by":"publisher","first-page":"e2","DOI":"10.1017\/qrd.2024.18","volume":"6","author":"F Johnsson","year":"2025","unstructured":"Johnsson F, Karag\u00f6l T, Karag\u00f6l A, Zhang S (2025) Structural bioinformatic study of six human olfactory receptors and their AlphaFold3 predicted water-soluble QTY variants and OR1A2 with an odorant octanoate and TAAR9 with spermidine. QRB discovery 6:e2","journal-title":"QRB discovery"},{"key":"2013_CR17","doi-asserted-by":"crossref","unstructured":"Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Hassabis,D. (2021). Highly accurate protein structure prediction with AlphaFold. nature, 596(7873),583\u2013589.","DOI":"10.1038\/s41586-021-03819-2"},{"issue":"3","key":"2013_CR18","doi-asserted-by":"publisher","first-page":"e0300340","DOI":"10.1371\/journal.pone.0300340","volume":"19","author":"T Karag\u00f6l","year":"2024","unstructured":"Karag\u00f6l T, Karag\u00f6l A, Zhang S (2024) Structural bioinformatics studies of serotonin, dopamine and norepinephrine transporters and their AlphaFold2 predicted water-soluble QTY variants and uncovering the natural mutations of L-> Q, I-> T, F-> Y and Q-> L, T-> I and Y-> F. PLoS ONE 19(3):e0300340","journal-title":"PLoS ONE"},{"issue":"4","key":"2013_CR19","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0289644","volume":"19","author":"A Karag\u00f6l","year":"2024","unstructured":"Karag\u00f6l A, Karag\u00f6l T, Smorodina E, Zhang S (2024) Structural bioinformatics studies of glutamate transporters and their AlphaFold2 predicted water-soluble QTY variants and uncovering the natural mutations of L-> Q, I-> T, F-> Y and Q-> L, T-> I and Y-> F. PLoS One 19(4):e0289644","journal-title":"PLoS One"},{"key":"2013_CR20","doi-asserted-by":"publisher","first-page":"zyag011","DOI":"10.1093\/intbio\/zyag011","volume":"18","author":"A Karag\u00f6l","year":"2026","unstructured":"Karag\u00f6l A, Karag\u00f6l T (2026) Adaptation to solvent environment in toll-like receptor 5: kernel-based evolutionary analysis of membrane-bound and soluble forms in Epinephelus coioides. Integr Biology 18:zyag011","journal-title":"Integr Biology"},{"issue":"10","key":"2013_CR21","doi-asserted-by":"publisher","first-page":"1965","DOI":"10.1007\/s11095-024-03769-0","volume":"41","author":"A Karag\u00f6l","year":"2024","unstructured":"Karag\u00f6l A, Karag\u00f6l T, Zhang S (2024) Molecular dynamic simulations reveal that water-soluble QTY-Variants of glutamate transporters EAA1, EAA2 and EAA3 retain the conformational characteristics of native transporters. Pharm Res 41(10):1965\u20131977","journal-title":"Pharm Res"},{"issue":"11","key":"2013_CR22","doi-asserted-by":"publisher","first-page":"2173","DOI":"10.1007\/s11095-024-03786-z","volume":"41","author":"A Karag\u00f6l","year":"2024","unstructured":"Karag\u00f6l A, Karag\u00f6l T, Li M, Zhang S (2024) Inhibitory Potential of the Truncated Isoforms on Glutamate Transporter Oligomerization Identified by Computational Analysis of Gene-Centric Isoform Maps. Pharm Res 41(11):2173\u20132187","journal-title":"Pharm Res"},{"issue":"1","key":"2013_CR23","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1007\/s00438-026-02444-w","volume":"301","author":"T Karag\u00f6l","year":"2026","unstructured":"Karag\u00f6l T, Karag\u00f6l A (2026) Microenvironmental pH and host-pathogen co-evolution potentially influence the structural architecture of junctional adhesion molecules. Mol Genet Genomics 301(1):118","journal-title":"Mol Genet Genomics"},{"issue":"260","key":"2013_CR24","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1080\/01621459.1952.10483441","volume":"47","author":"WH Kruskal","year":"1952","unstructured":"Kruskal WH, Wallis WA (1952) Use of ranks in one-criterion variance analysis. J Am Stat Assoc 47(260):583\u2013621","journal-title":"J Am Stat Assoc"},{"issue":"D1","key":"2013_CR25","doi-asserted-by":"publisher","first-page":"D980","DOI":"10.1093\/nar\/gkt1113","volume":"42","author":"MJ Landrum","year":"2014","unstructured":"Landrum MJ, Lee JM, Riley GR, Jang W, Rubinstein WS, Church DM, Maglott DR (2014) ClinVar: public archive of relationships among sequence variation and human phenotype. Nucleic Acids Res 42(D1):D980\u2013D985","journal-title":"Nucleic Acids Res"},{"issue":"41","key":"2013_CR26","doi-asserted-by":"publisher","first-page":"25445","DOI":"10.1073\/pnas.2002613117","volume":"117","author":"M Leander","year":"2020","unstructured":"Leander M, Yuan Y, Meger A, Cui Q, Raman S (2020) Functional plasticity and evolutionary adaptation of allosteric regulation. Proc Natl Acad Sci 117(41):25445\u201325454","journal-title":"Proc Natl Acad Sci"},{"issue":"2","key":"2013_CR27","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1016\/S0031-3203(02)00060-2","volume":"36","author":"A Likas","year":"2003","unstructured":"Likas A, Vlassis N, Verbeek JJ (2003) The global k-means clustering algorithm. Pattern Recogn 36(2):451\u2013461","journal-title":"Pattern Recogn"},{"issue":"1","key":"2013_CR28","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1109\/18.61115","volume":"37","author":"J Lin","year":"2002","unstructured":"Lin J (2002) Divergence measures based on the Shannon entropy. IEEE Trans Inf Theory 37(1):145\u2013151","journal-title":"IEEE Trans Inf Theory"},{"issue":"3","key":"2013_CR29","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1002\/prot.22372","volume":"76","author":"S Lukman","year":"2009","unstructured":"Lukman S, Grant GH (2009) A network of dynamically conserved residues deciphers the motions of maltose transporter. Proteins Struct Funct Bioinform 76(3):588\u2013597","journal-title":"Proteins Struct Funct Bioinform"},{"issue":"10","key":"2013_CR30","doi-asserted-by":"publisher","first-page":"5772","DOI":"10.1073\/pnas.1030237100","volume":"100","author":"B Ma","year":"2003","unstructured":"Ma B, Elkayam T, Wolfson H, Nussinov R (2003) Protein\u2013protein interactions: structurally conserved residues distinguish between binding sites and exposed protein surfaces. Proc Natl Acad Sci 100(10):5772\u20135777","journal-title":"Proc Natl Acad Sci"},{"issue":"9","key":"2013_CR31","first-page":"1","volume":"14","author":"W McKinney","year":"2011","unstructured":"McKinney W (2011) pandas: a foundational Python library for data analysis and statistics. Python high Perform Sci Comput 14(9):1\u20139","journal-title":"Python high Perform Sci Comput"},{"issue":"1","key":"2013_CR32","doi-asserted-by":"publisher","first-page":"13","DOI":"10.20982\/tqmp.04.1.p013","volume":"4","author":"N Nachar","year":"2008","unstructured":"Nachar N (2008) The Mann-Whitney U: A test for assessing whether two independent samples come from the same distribution. Tutorials Quant Methods Psychol 4(1):13\u201320","journal-title":"Tutorials Quant Methods Psychol"},{"key":"2013_CR33","doi-asserted-by":"crossref","unstructured":"Park, J. S., Park, M. C., Lee, K. Y., Goughnour, P. C., Jeong, S. J., Kim, H. S., Han, B. W. (2018). Unique N-terminal extension domain of human asparaginyl-tRNA synthetase elicits CCR3-mediated chemokine activity. International Journal of Biological Macromolecules, 120, 835\u2013845.","DOI":"10.1016\/j.ijbiomac.2018.08.171"},{"key":"2013_CR34","unstructured":"Pedregosa, F., Varoquaux, G., Gramfort, A., Michel, V., Thirion, B., Grisel, O., Duchesnay, \u00c9. (2011). Scikit-learn: Machine learning in Python. the Journal of machine Learning research, 12, 2825\u20132830."},{"key":"2013_CR35","doi-asserted-by":"crossref","unstructured":"Karag\u00f6l T, Karag\u00f6l A (2025) pH-Dependent Membrane Binding Specificity of Synaptogyrins 1\u20133 Provides Mechanistic Insights into Synaptic Vesicle Regulation and Neurological Disease. bioRxiv, 2025.","DOI":"10.1101\/2025.03.03.641025"},{"issue":"8","key":"2013_CR36","doi-asserted-by":"publisher","first-page":"1322","DOI":"10.1093\/bioinformatics\/btu829","volume":"31","author":"N Rego","year":"2015","unstructured":"Rego N, Koes D (2015) 3Dmol. js: molecular visualization with WebGL. Bioinformatics 31(8):1322\u20131324","journal-title":"Bioinformatics"},{"issue":"3","key":"2013_CR37","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1002\/wcms.1170","volume":"4","author":"C Riera","year":"2014","unstructured":"Riera C, Lois S, de la Cruz X (2014) Prediction of pathological mutations in proteins: the challenge of integrating sequence conservation and structure stability principles. WIREs Comput Mol Sci 4(3):249\u2013268","journal-title":"WIREs Comput Mol Sci"},{"issue":"15","key":"2013_CR38","doi-asserted-by":"publisher","first-page":"984","DOI":"10.1080\/08927022.2025.2562932","volume":"51","author":"A Sajeev-Sheeja","year":"2025","unstructured":"Sajeev-Sheeja A, Karag\u00f6l A, Karag\u00f6l T, Zhang S (2025) Molecular dynamics simulations and structural bioinformatics of bacterial integral alpha-helical membrane enzymes and their AlphaFold2-predicted water-soluble QTY analogues. Mol Simul 51(15):984\u2013998","journal-title":"Mol Simul"},{"key":"2013_CR39","doi-asserted-by":"crossref","unstructured":"Salda\u00f1o TE, Monzon AM, Parisi G, Fernandez-Alberti S (2016) Evolutionary conserved positions define protein conformational diversity. PLoS Comput Biol, 12(3), e1004775","DOI":"10.1371\/journal.pcbi.1004775"},{"key":"2013_CR40","doi-asserted-by":"crossref","unstructured":"Karag\u00f6l T, Karag\u00f6l A (2026) Serotonin, dopamine, and norepinephrine transporter assembly is selectively disrupted by a NET truncation isoform as revealed through near-million-atom simulations. bioRxiv, 2026\u20132003","DOI":"10.64898\/2026.03.25.714186"},{"key":"2013_CR41","doi-asserted-by":"crossref","unstructured":"Karag\u00f6l A, Karag\u00f6l T (2025) Splice Isoform Induced Selective Inhibition of Vesicular Monoamine Transporter Assembly Revealed by Multi-level Combinatorial Analysis. bioRxiv, 2025\u20132011","DOI":"10.1101\/2025.11.29.691296"},{"issue":"44","key":"2013_CR42","doi-asserted-by":"publisher","first-page":"13567","DOI":"10.1073\/pnas.1508584112","volume":"112","author":"L Sutto","year":"2015","unstructured":"Sutto L, Marsili S, Valencia A, Gervasio FL (2015) From residue coevolution to protein conformational ensembles and functional dynamics. Proc Natl Acad Sci 112(44):13567\u201313572","journal-title":"Proc Natl Acad Sci"},{"issue":"1","key":"2013_CR43","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1038\/s41597-024-03327-8","volume":"11","author":"H Tordai","year":"2024","unstructured":"Tordai H, Torres O, Csepi M, Padanyi R, Luk\u00e1cs GL, Heged\u0171s T (2024) Analysis of AlphaMissense data in different protein groups and structural context. Sci data 11(1):495","journal-title":"Sci data"},{"issue":"3","key":"2013_CR44","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1039\/B819720B","volume":"5","author":"CJ Tsai","year":"2009","unstructured":"Tsai CJ, Sol D, A., Nussinov R (2009) Protein allostery, signal transmission and dynamics: a classification scheme of allosteric mechanisms. Mol Biosyst 5(3):207\u2013216","journal-title":"Mol Biosyst"},{"key":"2013_CR45","doi-asserted-by":"crossref","unstructured":"The UniProt Consortium (2025) UniProt: the universal protein knowledgebase in 2025. Nucleic acids research 53, no. D1 (2025): D609-D617","DOI":"10.1093\/nar\/gkae1010"},{"issue":"D1","key":"2013_CR46","doi-asserted-by":"publisher","first-page":"D384","DOI":"10.1093\/nar\/gkad1084","volume":"52","author":"Y Vander Meersche","year":"2024","unstructured":"Vander Meersche Y, Cretin G, Gheeraert A, Gelly JC, Galochkina T (2024) ATLAS: protein flexibility description from atomistic molecular dynamics simulations. Nucleic Acids Res 52(D1):D384\u2013D392","journal-title":"Nucleic Acids Res"},{"key":"2013_CR47","doi-asserted-by":"crossref","unstructured":"Virtanen, P., Gommers, R., Oliphant, T. E., Haberland, M., Reddy, T., Cournapeau,D., Van Mulbregt, P. (2020). SciPy 1.0: fundamental algorithms for scientific computing in Python.Nature methods, 17(3), 261\u2013272","DOI":"10.1038\/s41592-020-0772-5"},{"key":"2013_CR48","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.105005","volume":"14","author":"M Xu","year":"2025","unstructured":"Xu M, Dantu SC, Garnett JA, Bonomo RA, Pandini A, Haider S (2025) Functionally important residues from graph analysis of coevolved dynamic couplings. eLife 14:RP105005","journal-title":"eLife"},{"key":"2013_CR49","doi-asserted-by":"crossref","unstructured":"Ye W, Wang Y, Wang Y (2015) Bioinformatics analysis reveals abundant short alpha-helices as a common structural feature of oomycete RxLR effector proteins. PLoS ONE, 10(8), e0135240","DOI":"10.1371\/journal.pone.0135240"},{"issue":"9","key":"2013_CR50","doi-asserted-by":"publisher","first-page":"3475","DOI":"10.1529\/biophysj.107.114835","volume":"94","author":"ON Yogurtcu","year":"2008","unstructured":"Yogurtcu ON, Erdemli SB, Nussinov R, Turkay M, Keskin O (2008) Restricted mobility of conserved residues in protein-protein interfaces in molecular simulations. Biophys J 94(9):3475\u20133485","journal-title":"Biophys J"},{"issue":"2","key":"2013_CR51","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1016\/j.jmb.2005.08.020","volume":"353","author":"P Yue","year":"2005","unstructured":"Yue P, Li Z, Moult J (2005) Loss of protein structure stability as a major causative factor in monogenic disease. J Mol Biol 353(2):459\u2013473","journal-title":"J Mol Biol"},{"key":"2013_CR52","volume-title":"Encyclopedia of biostatistics","author":"JH Zar","year":"2005","unstructured":"Zar JH (2005) Spearman rank correlation. Encyclopedia of biostatistics, vol 7"},{"issue":"37","key":"2013_CR53","doi-asserted-by":"publisher","first-page":"E8652","DOI":"10.1073\/pnas.1811031115","volume":"115","author":"S Zhang","year":"2018","unstructured":"Zhang S, Tao F, Qing R, Tang H, Skuhersky M, Corin K, Maertens B (2018) QTY code enables design of detergent-free chemokine receptors that retain ligand-binding activities. Proc Natl Acad Sci 115(37):E8652\u2013E8659","journal-title":"Proc Natl Acad Sci"},{"issue":"4","key":"2013_CR54","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1093\/clinchem\/39.4.561","volume":"39","author":"MH Zweig","year":"1993","unstructured":"Zweig MH, Campbell G (1993) Receiver-operating characteristic (ROC) plots: a fundamental evaluation tool in clinical medicine. Clin Chem 39(4):561\u2013577","journal-title":"Clin Chem"},{"key":"2013_CR55","unstructured":"R Core Team (2016) R: A Language and Environment for Statistical Computing. Vienna, Austria. Available from: https:\/\/www.R-project.org\/"},{"key":"2013_CR56","unstructured":"Schr\u00f6dinger LLC (2024) The PyMOL Molecular Graphics System, Version 3. https:\/\/www.pymol.org Accessed 30 March 2024"}],"container-title":["Functional & Integrative Genomics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10142-026-02013-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10142-026-02013-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10142-026-02013-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T01:09:27Z","timestamp":1787360967000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10142-026-02013-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,22]]},"references-count":56,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,12]]}},"alternative-id":["2013"],"URL":"https:\/\/doi.org\/10.1007\/s10142-026-02013-9","relation":{},"ISSN":["1438-793X","1438-7948"],"issn-type":[{"value":"1438-793X","type":"print"},{"value":"1438-7948","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,22]]},"assertion":[{"value":"26 February 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 July 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 August 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 August 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Ethics approval was not required for this computational study because this study did not involve animal subjects, human participants, and identifiable data.","order":1,"name":"Ethics","label":"Ethical approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable. This computational study did not involve human participants.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":3,"name":"Ethics","label":"Clinical trial number","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable. This computational study did not involve human participants.","order":4,"name":"Ethics","label":"Consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":5,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"228"}}