{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T11:50:05Z","timestamp":1768477805633,"version":"3.49.0"},"reference-count":99,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,1,28]],"date-time":"2024-01-28T00:00:00Z","timestamp":1706400000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Dyskeratosis Congenita (DC) is a multisystem disorder intrinsically associated with telomere dysfunction, leading to bone marrow failure (BMF). Although the pathology of DC is largely driven by mutations in telomere-associated genes, the implications of gene fusions, which emerge due to telomere-induced genomic instability, remain unexplored. We meticulously analyzed gene fusions in RNA-Seq data from DC patients to provide deeper insights into DC\u2019s progression. The most significant DC-specific gene fusions were subsequently put through in silico assessments to ascertain biophysical and structural attributes, including charge patterning, inherent disorder, and propensity for self-association. Selected candidates were then analyzed using deep learning-powered structural predictions and molecular dynamics simulations to gauge their potential for forming higher-order oligomers. Our exploration revealed that genes participating in fusion events play crucial roles in upholding genomic stability, facilitating hematopoiesis, and suppressing tumors. Notably, our analysis spotlighted a particularly disordered polyampholyte fusion protein that exhibits robust higher-order oligomerization dynamics. To conclude, this research underscores the potential significance of several high-confidence gene fusions in the progression of BMF in DC, particularly through the dysregulation of genomic stability, hematopoiesis, and tumor suppression. Additionally, we propose that these fusion proteins might hold a detrimental role, specifically in inducing proteotoxicity-driven hematopoietic disruptions.<\/jats:p>","DOI":"10.3390\/ijms25031606","type":"journal-article","created":{"date-parts":[[2024,1,29]],"date-time":"2024-01-29T04:57:07Z","timestamp":1706504227000},"page":"1606","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Linking Gene Fusions to Bone Marrow Failure and Malignant Transformation in Dyskeratosis Congenita"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0218-7721","authenticated-orcid":false,"given":"\u00d6mer","family":"G\u00fcll\u00fcl\u00fc","sequence":"first","affiliation":[{"name":"Department of Structural Biology, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin E.","family":"Mayer","sequence":"additional","affiliation":[{"name":"Computational Biology & Simulation, Technische Universit\u00e4t Darmstadt, 64287 Darmstadt, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fran Ba\u010di\u0107","family":"Toplek","sequence":"additional","affiliation":[{"name":"Dipartimento di Bioscienze, Universit\u00e0 degli Studi di Milano, 20133 Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,28]]},"reference":[{"key":"ref_1","first-page":"157","article-title":"The diagnosis and treatment of dyskeratosis congenita: A review","volume":"5","year":"2014","journal-title":"J. Blood Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1038\/s41525-021-00198-5","article-title":"Telomere biology disorders","volume":"6","author":"Kam","year":"2021","journal-title":"NPJ Genom. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1159\/000251605","article-title":"Dyskeratosis congenita Zinsser-Cole-Engmann form with abnormal karyotype","volume":"148","author":"Gomez","year":"1974","journal-title":"Dermatologica"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3090","DOI":"10.1182\/blood.V80.12.3090.3090","article-title":"Dyskeratosis congenita fibroblasts are abnormal and have unbalanced chromosomal rearrangements","volume":"80","author":"Dokal","year":"1992","journal-title":"Blood"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1002\/ajmg.1320420219","article-title":"Chromosome abnormalities in cell cultures derived from the leukoplakia of a female patient with dyskeratosis congenita","volume":"42","author":"Kehrer","year":"1992","journal-title":"Am. J. Med. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1002\/ajmg.1320340433","article-title":"Chromosome abnormalities in dyskeratosis congenita","volume":"34","author":"Scappaticci","year":"1989","journal-title":"Am. J. Med. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.celrep.2018.03.050","article-title":"Driver Fusions and Their Implications in the Development and Treatment of Human Cancers","volume":"23","author":"Gao","year":"2018","journal-title":"Cell Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1101\/gr.257246.119","article-title":"Accurate and efficient detection of gene fusions from RNA sequencing data","volume":"31","author":"Uhrig","year":"2021","journal-title":"Genome Res."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Emily, N., Brian, R., and Valerie, K. (2022). The oncogenic fusion protein TAZ-CAMTA1 promotes genomic instability and senescence through hypertranscription. bioRxiv.","DOI":"10.1101\/2022.12.01.518701"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Price, J.C., Pollock, L.M., Rudd, M.L., Fogoros, S.K., Mohamed, H., Hanigan, C.L., Le Gallo, M., NIH Intramural Sequencing Center (NISC) Comparative Sequencing Program, Zhang, S., and Cruz, P. (2014). Sequencing of candidate chromosome instability genes in endometrial cancers reveals somatic mutations in ESCO1, CHTF18, and MRE11A. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0063313"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2136","DOI":"10.1101\/gad.306084.117","article-title":"ESCO1\/2\u2019s roles in chromosome structure and interphase chromatin organization","volume":"31","author":"Kawasumi","year":"2017","journal-title":"Genes. Dev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1038\/ncomms2008","article-title":"FOXO3 signalling links ATM to the p53 apoptotic pathway following DNA damage","volume":"3","author":"Chung","year":"2012","journal-title":"Nat. Commun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3005","DOI":"10.1074\/jbc.M116.769455","article-title":"FOXO3 Transcription Factor Is Essential for Protecting Hematopoietic Stem and Progenitor Cells from Oxidative DNA Damage","volume":"292","author":"Bigarella","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e13184","DOI":"10.1111\/acel.13184","article-title":"FOXO3a acts to suppress DNA double-strand break-induced mutations","volume":"19","author":"White","year":"2020","journal-title":"Aging Cell"},{"key":"ref_15","unstructured":"George, G., Karolina, K., Muzamil, M.K., Peter, T., Beate, N., Emma, L., and Rainer, P. (2022). The Golgi complex is a regulatory hub for homologous recombination-mediated DNA repair. bioRxiv."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"106107","DOI":"10.1016\/j.isci.2023.106107","article-title":"Microtubule-associated proteins MAP7 and MAP7D1 promote DNA double-strand break repair in the G1 cell cycle phase","volume":"26","author":"Dullovi","year":"2023","journal-title":"iScience"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e104543","DOI":"10.15252\/embj.2020104543","article-title":"DNA polymerase zeta contributes to heterochromatin replication to prevent genome instability","volume":"40","author":"Tomida","year":"2021","journal-title":"EMBO J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1016\/j.celrep.2013.03.040","article-title":"Chromosomal instability triggered by Rrm2b loss leads to IL-6 secretion and plasmacytic neoplasms","volume":"3","author":"Chang","year":"2013","journal-title":"Cell Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1158\/0008-5472.CAN-19-2149","article-title":"The Deubiquitinase USP38 Promotes NHEJ Repair through Regulation of HDAC1 Activity and Regulates Cancer Cell Response to Genotoxic Insults","volume":"80","author":"Yang","year":"2020","journal-title":"Cancer Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4079","DOI":"10.1083\/jcb.201902046","article-title":"Vimentin protects cells against nuclear rupture and DNA damage during migration","volume":"218","author":"Patteson","year":"2019","journal-title":"J. Cell Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.celrep.2014.03.030","article-title":"The RBBP6\/ZBTB38\/MCM10 Axis Regulates DNA Replication and Common Fragile Site Stability","volume":"7","author":"Miotto","year":"2014","journal-title":"Cell Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"29974","DOI":"10.1074\/jbc.M115.678003","article-title":"Cyclic Nucleotide-dependent Protein Kinases Target ARHGAP17 and ARHGEF6 Complexes in Platelets","volume":"290","author":"Nagy","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2845","DOI":"10.1182\/blood-2009-07-234377","article-title":"Inactivation of LEF1 in T-cell acute lymphoblastic leukemia","volume":"115","author":"Gutierrez","year":"2010","journal-title":"Blood"},{"key":"ref_24","first-page":"269","article-title":"LRRFIP1 expression triggers platelet agglutination by enhancing alphaIIbbeta3 expression","volume":"18","author":"Yin","year":"2019","journal-title":"Exp. Ther. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4646","DOI":"10.1182\/blood-2010-04-280925","article-title":"Transcription profiling in human platelets reveals LRRFIP1 as a novel protein regulating platelet function","volume":"116","author":"Goodall","year":"2010","journal-title":"Blood"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1074\/mcp.M112.023168","article-title":"Platelet proteome analysis reveals integrin-dependent aggregation defects in patients with myelodysplastic syndromes","volume":"12","author":"Frobel","year":"2013","journal-title":"Mol. Cell Proteom."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1038\/s41408-021-00504-5","article-title":"Fusion gene map of acute leukemia revealed by transcriptome sequencing of a consecutive cohort of 1000 cases in a single center","volume":"11","author":"Chen","year":"2021","journal-title":"Blood Cancer J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"19","DOI":"10.29245\/2578-3009\/2018\/2.1130","article-title":"Prothymosin \u03b1, a protein implicated in the proliferation and survival of lymphocytes","volume":"2","author":"Freire","year":"2018","journal-title":"J. Immunol. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1182\/blood.2020005382","article-title":"Thrombospondin-1 promotes hemostasis through modulation of cAMP signaling in blood platelets","volume":"137","author":"Aburima","year":"2021","journal-title":"Blood"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1038\/nrc3947","article-title":"The emerging complexity of gene fusions in cancer","volume":"15","author":"Mertens","year":"2015","journal-title":"Nat. Rev. Cancer"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2138","DOI":"10.1159\/000489543","article-title":"Tumor Suppressive Role of ARHGAP17 in Colon Cancer Through Wnt\/beta-Catenin Signaling","volume":"46","author":"Pan","year":"2018","journal-title":"Cell Physiol. Biochem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"109882","DOI":"10.1016\/j.cellsig.2020.109882","article-title":"CAMTA1, a novel antitumor gene, regulates proliferation and the cell cycle in glioma by inhibiting AKT phosphorylation","volume":"79","author":"He","year":"2021","journal-title":"Cell Signal"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3142","DOI":"10.1158\/0008-5472.CAN-10-3014","article-title":"CAMTA1, a 1p36 tumor suppressor candidate, inhibits growth and activates differentiation programs in neuroblastoma cells","volume":"71","author":"Henrich","year":"2011","journal-title":"Cancer Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1038\/s41590-021-00896-3","article-title":"The tumor suppressor kinase DAPK3 drives tumor-intrinsic immunity through the STING-IFN-beta pathway","volume":"22","author":"Takahashi","year":"2021","journal-title":"Nat. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.tcb.2008.07.004","article-title":"Unravelling the tumor-suppressive functions of FOXO proteins","volume":"18","author":"Dansen","year":"2008","journal-title":"Trends Cell Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1770","DOI":"10.1038\/onc.2015.241","article-title":"Heat-shock factor 2 is a suppressor of prostate cancer invasion","volume":"35","author":"Bjork","year":"2016","journal-title":"Oncogene"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"845488","DOI":"10.3389\/fimmu.2022.845488","article-title":"Oncogenic and Tumor Suppressor Functions for Lymphoid Enhancer Factor 1 in E2a(-\/-) T Acute Lymphoblastic Leukemia","volume":"13","author":"Carr","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"802941","DOI":"10.3389\/fonc.2022.802941","article-title":"Low Level of PALMD Contributes to the Metastasis of Uveal Melanoma","volume":"12","author":"Cai","year":"2022","journal-title":"Front. Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e99179","DOI":"10.15252\/embj.201899179","article-title":"Tumor suppressor PNRC1 blocks rRNA maturation by recruiting the decapping complex to the nucleolus","volume":"37","author":"Gaviraghi","year":"2018","journal-title":"EMBO J."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.bbrc.2012.04.138","article-title":"Downregulation of tumor suppressor QKI in gastric cancer and its implication in cancer prognosis","volume":"422","author":"Bian","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3261","DOI":"10.1007\/s00262-021-02913-8","article-title":"RB1CC1 functions as a tumor-suppressing gene in renal cell carcinoma via suppression of PYK2 activity and disruption of TAZ-mediated PDL1 transcription activation","volume":"70","author":"Chen","year":"2021","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1186\/s13046-019-1111-5","article-title":"The RNA binding protein RBMS3 inhibits the metastasis of breast cancer by regulating Twist1 expression","volume":"38","author":"Zhu","year":"2019","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1002\/jcb.24964","article-title":"RGS2 suppresses breast cancer cell growth via a MCPIP1-dependent pathway","volume":"116","author":"Lyu","year":"2015","journal-title":"J. Cell Biochem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1038\/s41419-021-04278-3","article-title":"ZBTB38 suppresses prostate cancer cell proliferation and migration via directly promoting DKK1 expression","volume":"12","author":"Ding","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"6549","DOI":"10.1182\/blood-2008-12-192880","article-title":"Cancer in dyskeratosis congenita","volume":"113","author":"Alter","year":"2009","journal-title":"Blood"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"12119","DOI":"10.1093\/nar\/gkab1015","article-title":"The human telomeric proteome during telomere replication","volume":"49","author":"Lin","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1016\/j.molcel.2016.07.008","article-title":"Molecular Principles of Gene Fusion Mediated Rewiring of Protein Interaction Networks in Cancer","volume":"63","author":"Latysheva","year":"2016","journal-title":"Mol. Cell"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1097\/MOH.0000000000000591","article-title":"Hematopoietic stem cell regulation by the proteostasis network","volume":"27","author":"Chua","year":"2020","journal-title":"Curr. Opin. Hematol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.3324\/haematol.2019.233056","article-title":"The Hsp70 chaperone system: Distinct roles in erythrocyte formation and maintenance","volume":"106","author":"Mathangasinghe","year":"2021","journal-title":"Haematologica"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"13392","DOI":"10.1073\/pnas.1304749110","article-title":"Conformations of intrinsically disordered proteins are influenced by linear sequence distributions of oppositely charged residues","volume":"110","author":"Das","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.bpj.2016.11.3200","article-title":"CIDER: Resources to Analyze Sequence-Ensemble Relationships of Intrinsically Disordered Proteins","volume":"112","author":"Holehouse","year":"2017","journal-title":"Biophys. J."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1089\/jir.2010.0017","article-title":"Leucine-rich repeat (in Flightless I) interacting protein-1 regulates a rapid type I interferon response","volume":"30","author":"Bagashev","year":"2010","journal-title":"J. Interferon Cytokine Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/bs.vh.2016.04.008","article-title":"Prothymosin Alpha and Immune Responses: Are We Close to Potential Clinical Applications?","volume":"102","author":"Samara","year":"2016","journal-title":"Vitam. Horm."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1038\/s41594-022-00849-w","article-title":"A structural biology community assessment of AlphaFold2 applications","volume":"29","author":"Akdel","year":"2022","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Radom, F., Pl\u00fcckthun, A., and Paci, E. (2018). Assessment of ab initio models of protein complexes by molecular dynamics. PLoS Comput. Biol., 14.","DOI":"10.1371\/journal.pcbi.1006182"},{"key":"ref_56","first-page":"564","article-title":"Aberrant phase separation and nucleolar dysfunction in rare genetic diseases","volume":"614","author":"Mensah","year":"2023","journal-title":"Nature"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/S0014-5793(02)02572-3","article-title":"Amyloid fibrils from the mammalian protein prothymosin alpha","volume":"517","author":"Pavlov","year":"2002","journal-title":"FEBS Lett."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"6247","DOI":"10.1182\/blood-2011-07-328880","article-title":"NUP98 gene fusions and hematopoietic malignancies: Common themes and new biologic insights","volume":"118","author":"Gough","year":"2011","journal-title":"Blood"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e0724","DOI":"10.1097\/MD.0000000000010724","article-title":"A case report of heterozygous TINF2 gene mutation associated with pulmonary fibrosis in a patient with dyskeratosis congenita","volume":"97","author":"Du","year":"2018","journal-title":"Medicine"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.1183\/09031936.00149113","article-title":"Pulmonary fibrosis in dyskeratosis congenita with TINF2 gene mutation","volume":"42","author":"Fukuhara","year":"2013","journal-title":"Eur. Respir. J."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.humpath.2014.10.003","article-title":"Pulmonary fibrosis in dyskeratosis congenita: Report of 2 cases","volume":"46","author":"Dvorak","year":"2015","journal-title":"Hum. Pathol."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Giri, N., Lee, R., Faro, A., Huddleston, C.B., White, F.V., Alter, B.P., and Savage, S.A. (2011). Lung transplantation for pulmonary fibrosis in dyskeratosis congenita: Case Report and systematic literature review. BMC Blood Disord., 11.","DOI":"10.1186\/1471-2326-11-3"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1038\/ncb3580","article-title":"Local lung hypoxia determines epithelial fate decisions during alveolar regeneration","volume":"19","author":"Xi","year":"2017","journal-title":"Nat. Cell Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e109","DOI":"10.1002\/imt2.109","article-title":"shinyCircos-V2.0: Leveraging the creation of Circos plot with enhanced usability and advanced features","volume":"2","author":"Wang","year":"2023","journal-title":"iMeta"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1002\/pro.4218","article-title":"PANTHER: Making genome-scale phylogenetics accessible to all","volume":"31","author":"Thomas","year":"2022","journal-title":"Protein Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"W199","DOI":"10.1093\/nar\/gkz401","article-title":"WebGestalt 2019: Gene set analysis toolkit with revamped UIs and APIs","volume":"47","author":"Liao","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"D607","DOI":"10.1093\/nar\/gky1131","article-title":"STRING v11: Protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets","volume":"47","author":"Szklarczyk","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Grill, S., and Nandakumar, J. (2021). Molecular mechanisms of telomere biology disorders. J. Biol. Chem., 296.","DOI":"10.1074\/jbc.REV120.014017"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"101457","DOI":"10.1016\/j.cocis.2021.101457","article-title":"Polyampholyte physics: Liquid\u2013liquid phase separation and biological condensates","volume":"54","author":"Dinic","year":"2021","journal-title":"Curr. Opin. Colloid Interface Sci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"W337","DOI":"10.1093\/nar\/gkac386","article-title":"FuzDrop on AlphaFold: Visualizing the sequence-dependent propensity of liquid-liquid phase separation and aggregation of proteins","volume":"50","author":"Hatos","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"178101","DOI":"10.1103\/PhysRevLett.117.178101","article-title":"Sequence-Specific Polyampholyte Phase Separation in Membraneless Organelles","volume":"117","author":"Lin","year":"2016","journal-title":"Phys. Rev. Lett."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"e2019053118","DOI":"10.1073\/pnas.2019053118","article-title":"Learning the molecular grammar of protein condensates from sequence determinants and embeddings","volume":"118","author":"Saar","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly accurate protein structure prediction with AlphaFold","volume":"596","author":"Jumper","year":"2021","journal-title":"Nature"},{"key":"ref_74","unstructured":"Schrodinger, LLC. (2023). The PyMOL Molecular Graphics System, (Unpublished)."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.softx.2015.06.001","article-title":"GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers","volume":"1\u20132","author":"Abraham","year":"2015","journal-title":"SoftwareX"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"P\u00e1ll, S., Abraham, M.J., Kutzner, C., Hess, B., and Lindahl, E. (2014, January 2\u20133). Tackling Exascale Software Challenges in Molecular Dynamics Simulations with GROMACS. Proceedings of the International Conference on Exascale Applications and Software, Stockholm, Sweden.","DOI":"10.1007\/978-3-319-15976-8_1"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1093\/bioinformatics\/btt055","article-title":"GROMACS 4.5: A high-throughput and highly parallel open source molecular simulation toolkit","volume":"29","author":"Pronk","year":"2013","journal-title":"Bioinformatics"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1021\/ct700301q","article-title":"GROMACS 4:\u2009 Algorithms for Highly Efficient, Load-Balanced, and Scalable Molecular Simulation","volume":"4","author":"Hess","year":"2008","journal-title":"J. Chem. Theory Comput."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1002\/jcc.20291","article-title":"GROMACS: Fast, flexible, and free","volume":"26","author":"Lindahl","year":"2005","journal-title":"J. Comput. Chem."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1007\/s008940100045","article-title":"GROMACS 3.0: A package for molecular simulation and trajectory analysis","volume":"7","author":"Lindahl","year":"2001","journal-title":"Mol. Model. Annu."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/0010-4655(95)00042-E","article-title":"GROMACS: A message-passing parallel molecular dynamics implementation","volume":"91","author":"Berendsen","year":"1995","journal-title":"Comput. Phys. Commun."},{"key":"ref_82","unstructured":"Lindahl, E., Abraham, M.J., Hess, B., and van der Spoel, D. (2022). GROMACS 2021.5 Source Code, Zenodo. 2021.5."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1038\/nmeth.4067","article-title":"CHARMM36m: An improved force field for folded and intrinsically disordered proteins","volume":"14","author":"Huang","year":"2017","journal-title":"Nat. Methods"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1145\/279232.279236","article-title":"Algorithm 778: L-BFGS-B: Fortran subroutines for large-scale bound-constrained optimization","volume":"23","author":"Zhu","year":"1997","journal-title":"ACM Trans. Math. Softw."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1137\/0916069","article-title":"A Limited Memory Algorithm for Bound Constrained Optimization","volume":"16","author":"Byrd","year":"1995","journal-title":"SIAM J. Sci. Comput."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"114107","DOI":"10.1063\/5.0020514","article-title":"Pressure control using stochastic cell rescaling","volume":"153","author":"Bernetti","year":"2020","journal-title":"J. Chem. Phys."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Kunzmann, P., and Hamacher, K. (2018). Biotite: A unifying open source computational biology framework in Python. BMC Bioinform., 19.","DOI":"10.1186\/s12859-018-2367-z"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Kunzmann, P., M\u00fcller, T.D., Greil, M., Krumbach, J.H., Anter, J.M., Bauer, D., Islam, F., and Hamacher, K. (2023). Biotite: New tools for a versatile Python bioinformatics library. BMC Bioinform., 24.","DOI":"10.1186\/s12859-023-05345-6"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/s41592-019-0686-2","article-title":"SciPy 1.0: Fundamental algorithms for scientific computing in Python","volume":"17","author":"Virtanen","year":"2020","journal-title":"Nat. Methods"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/s41586-020-2649-2","article-title":"Array programming with NumPy","volume":"585","author":"Harris","year":"2020","journal-title":"Nature"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1109\/MCSE.2007.55","article-title":"Matplotlib: A 2D Graphics Environment","volume":"9","author":"Hunter","year":"2007","journal-title":"Comput. Sci. Eng."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.mrfmmm.2011.06.008","article-title":"Dyskeratosis congenita as a disorder of telomere maintenance","volume":"730","author":"Nelson","year":"2012","journal-title":"Mutat. Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1134\/S0026893318020048","article-title":"Identification of Fusion Transcripts in Leukemic Cells by Whole-Transcriptome Sequencing","volume":"52","author":"Ikonnikova","year":"2018","journal-title":"Mol. Biol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1007\/s10637-020-00984-5","article-title":"A novel LRRFIP1-ALK fusion in inflammatory myofibroblastic tumor of hip and response to crizotinib","volume":"39","author":"Liu","year":"2021","journal-title":"Investig. New Drugs"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"7174","DOI":"10.1038\/ncomms8174","article-title":"Activating MET kinase rearrangements in melanoma and Spitz tumours","volume":"6","author":"Yeh","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1038\/leu.2009.79","article-title":"LRRFIP1, a new FGFR1 partner gene associated with 8p11 myeloproliferative syndrome","volume":"23","author":"Soler","year":"2009","journal-title":"Leukemia"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"15009","DOI":"10.1021\/bi990752+","article-title":"Natively unfolded human prothymosin alpha adopts partially folded collapsed conformation at acidic pH","volume":"38","author":"Uversky","year":"1999","journal-title":"Biochemistry"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"9589","DOI":"10.1021\/acs.jpclett.2c01972","article-title":"pH Induced Switch in the Conformational Ensemble of Intrinsically Disordered Protein Prothymosin-alpha and Its Implications for Amyloid Fibril Formation","volume":"13","author":"Baidya","year":"2022","journal-title":"J. Phys. Chem. Lett."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Haas, B.J., Dobin, A., Li, B., Stransky, N., Pochet, N., and Regev, A. (2019). Accuracy assessment of fusion transcript detection via read-mapping and de novo fusion transcript assembly-based methods. Genome Biol., 20.","DOI":"10.1186\/s13059-019-1842-9"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/3\/1606\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:50:32Z","timestamp":1760104232000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/3\/1606"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,28]]},"references-count":99,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,2]]}},"alternative-id":["ijms25031606"],"URL":"https:\/\/doi.org\/10.3390\/ijms25031606","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,28]]}}}