@article{MTMT:34563187,
	title = {Decreased Expression of Placental Proteins in Recurrent Pregnancy Loss: Functional Relevance and Diagnostic Value},
	url = {https://m2.mtmt.hu/api/publication/34563187},
	author = {Tóth, Eszter and Györffy, Dániel and Posta, Máté and Hupuczi, Petronella and Balogh, Andrea and Szalai, Gábor and Orosz, Gergő Balázs and Orosz, László and Szilágyi, András and Oravecz, Orsolya and Veress, Lajos and Nagy, Sándor and Török, Olga and Murthi, Padma and Erez, Offer and Papp, Zoltán and Ács, Nándor and Than, Nándor Gábor},
	doi = {10.3390/ijms25031865},
	journal-iso = {INT J MOL SCI},
	journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
	volume = {25},
	unique-id = {34563187},
	issn = {1661-6596},
	abstract = {Miscarriages affect 50–70% of all conceptions and 15–20% of clinically recognized pregnancies. Recurrent pregnancy loss (RPL, ≥2 miscarriages) affects 1–5% of recognized pregnancies. Nevertheless, our knowledge about the etiologies and pathophysiology of RPL is incomplete, and thus, reliable diagnostic/preventive tools are not yet available. Here, we aimed to define the diagnostic value of three placental proteins for RPL: human chorionic gonadotropin free beta-subunit (free-β-hCG), pregnancy-associated plasma protein-A (PAPP-A), and placental growth factor (PlGF). Blood samples were collected from women with RPL (n = 14) and controls undergoing elective termination of pregnancy (n = 30) at the time of surgery. Maternal serum protein concentrations were measured by BRAHMS KRYPTOR Analyzer. Daily multiple of median (dMoM) values were calculated for gestational age-specific normalization. To obtain classifiers, logistic regression analysis was performed, and ROC curves were calculated. There were differences in changes of maternal serum protein concentrations with advancing healthy gestation. Between 6 and 13 weeks, women with RPL had lower concentrations and dMoMs of free β-hCG, PAPP-A, and PlGF than controls. PAPP-A dMoM had the best discriminative properties (AUC = 0.880). Between 9 and 13 weeks, discriminative properties of all protein dMoMs were excellent (free β-hCG: AUC = 0.975; PAPP-A: AUC = 0.998; PlGF: AUC = 0.924). In conclusion, free-β-hCG and PAPP-A are valuable biomarkers for RPL, especially between 9 and 13 weeks. Their decreased concentrations indicate the deterioration of placental functions, while lower PlGF levels indicate problems with placental angiogenesis after 9 weeks.},
	year = {2024},
	eissn = {1422-0067},
	orcid-numbers = {Tóth, Eszter/0000-0001-7149-1482; Balogh, Andrea/0000-0003-0322-1522; Szilágyi, András/0000-0002-1773-6861; Murthi, Padma/0000-0003-2535-5134; Ács, Nándor/0000-0002-1919-1869}
}

@article{MTMT:34477407,
	title = {Classification of preeclampsia according to molecular clusters with the goal of achieving personalized prevention},
	url = {https://m2.mtmt.hu/api/publication/34477407},
	author = {Than, Nándor Gábor and Romero, Roberto and Posta, Máté and Györffy, Dániel and Szalai, Gábor and Rossi, Simona W and Szilágyi, András and Hupuczi, Petronella and Nagy, Sándor and Török, Olga and Tarca, Adi L and Erez, Offer and Ács, Nándor and Papp, Zoltán},
	doi = {10.1016/j.jri.2023.104172},
	journal-iso = {J REPROD IMMUNOL},
	journal = {JOURNAL OF REPRODUCTIVE IMMUNOLOGY},
	volume = {161},
	unique-id = {34477407},
	issn = {0165-0378},
	abstract = {The prevention of pre-eclampsia is difficult due to the syndromic nature and multiple underlying mechanisms of this severe complication of pregnancy. The current clinical distinction between early- and late-onset disease, although clinically useful, does not reflect the true nature and complexity of the pathologic processes leading to pre-eclampsia. The current gaps in knowledge on the heterogeneous molecular pathways of this syndrome and the lack of adequate, specific diagnostic methods are major obstacles to early screening and tailored preventive strategies. The development of novel diagnostic tools for detecting the activation of the identified disease pathways would enable early, accurate screening and personalized preventive therapies. We implemented a holistic approach that includes the utilization of different proteomic profiling methods of maternal plasma samples collected from various ethnic populations and the application of systems biology analysis to plasma proteomic, maternal demographic, clinical characteristic, and placental histopathologic data. This approach enabled the identification of four molecular subclasses of pre-eclampsia in which distinct and shared disease mechanisms are activated. The current review summarizes the results and conclusions from these studies and the research and clinical implications of our findings.},
	keywords = {proteomics; personalized medicine; Screening; Prenatal Diagnosis; liquid biopsy; Extracellular matrix-related pre-eclampsia; Maternal anti-fetal rejection-type pre-eclampsia; Metabolic pre-eclampsia; Placental pre-eclampsia},
	year = {2024},
	eissn = {1872-7603},
	orcid-numbers = {Szilágyi, András/0000-0002-1773-6861; Ács, Nándor/0000-0002-1919-1869}
}

@article{MTMT:34410484,
	title = {A Kinetic Transition Network Model Reveals the Diversity of Protein Dimer Formation Mechanisms},
	url = {https://m2.mtmt.hu/api/publication/34410484},
	author = {Györffy, Dániel and Závodszky, Péter and Szilágyi, András},
	doi = {10.3390/biom13121708},
	journal-iso = {BIOMOLECULES},
	journal = {BIOMOLECULES},
	volume = {13},
	unique-id = {34410484},
	issn = {2218-273X},
	abstract = {Protein homodimers have been classified as three-state or two-state dimers depending on whether a folded monomer forms before association, but the details of the folding–binding mechanisms are poorly understood. Kinetic transition networks of conformational states have provided insight into the folding mechanisms of monomeric proteins, but extending such a network to two protein chains is challenging as all the relative positions and orientations of the chains need to be included, greatly increasing the number of degrees of freedom. Here, we present a simplification of the problem by grouping all states of the two chains into two layers: a dissociated and an associated layer. We combined our two-layer approach with the Wako–Saito–Muñoz–Eaton method and used Transition Path Theory to investigate the dimer formation kinetics of eight homodimers. The analysis reveals a remarkable diversity of dimer formation mechanisms. Induced folding, conformational selection, and rigid docking are often simultaneously at work, and their contribution depends on the protein concentration. Pre-folded structural elements are always present at the moment of association, and asymmetric binding mechanisms are common. Our two-layer network approach can be combined with various methods that generate discrete states, yielding new insights into the kinetics and pathways of flexible binding processes.},
	year = {2023},
	eissn = {2218-273X},
	orcid-numbers = {Szilágyi, András/0000-0002-1773-6861}
}

@article{MTMT:33186504,
	title = {Molecular subclasses of preeclampsia characterized by a longitudinal maternal proteomics study: distinct biomarkers, disease pathways and options for prevention},
	url = {https://m2.mtmt.hu/api/publication/33186504},
	author = {Than, Nándor Gábor and Romero, Roberto and Györffy, Dániel and Posta, Máté and Bhatti, Gaurav and Done, Bogdan and Chaemsaithong, Piya and Jung, Eunjung and Suksai, Manaphat and Gotsch, Francesca and Gallo, Dahiana M. and Bosco, Mariachiara and Kim, Bomi and Kim, Yeon Mee and Chaiworapongsa, Tinnakorn and Rossi, Simona W. and Szilágyi, András and Erez, Offer and Tarca, Adi L. and Papp, Zoltán},
	doi = {10.1515/jpm-2022-0433},
	journal-iso = {J PERINAT MED},
	journal = {JOURNAL OF PERINATAL MEDICINE},
	volume = {51},
	unique-id = {33186504},
	issn = {0300-5577},
	year = {2023},
	eissn = {1619-3997},
	pages = {51-68},
	orcid-numbers = {Szilágyi, András/0000-0002-1773-6861}
}

@article{MTMT:32760816,
	title = {Early pathways, biomarkers, and four distinct molecular subclasses of preeclampsia: The intersection of clinical, pathological, and high-dimensional biology studies},
	url = {https://m2.mtmt.hu/api/publication/32760816},
	author = {Than, Nándor Gábor and Posta, Máté and Györffy, Dániel and Orosz, László and Orosz, Gergő Balázs and Rossi, Simona W. and Ambrus-Aikelin, Géza and Szilágyi, András and Nagy, Sándor and Hupuczi, Petronella and Török, Olga and Tarca, Adi L. and Erez, Offer and Papp, Zoltán and Romero, Roberto},
	doi = {10.1016/j.placenta.2022.03.009},
	journal-iso = {PLACENTA},
	journal = {PLACENTA},
	volume = {125},
	unique-id = {32760816},
	issn = {0143-4004},
	year = {2022},
	eissn = {1532-3102},
	pages = {10-19},
	orcid-numbers = {Szilágyi, András/0000-0002-1773-6861; Tarca, Adi L./0000-0003-1712-7588}
}

@article{MTMT:32725682,
	title = {A praeeclampsia korai betegségútvonalai, biomarkerei és négy különböző molekuláris alosztálya},
	url = {https://m2.mtmt.hu/api/publication/32725682},
	author = {Than, Nándor Gábor and Posta, Máté and Györffy, Dániel and Orosz, László and Orosz, Gergő and Rossi, Simona Wilma and Ambrus-Aikelin, Géza and Szilágyi, András and Nagy, Sándor and Hupuczi, Petronella and Török, Olga and Tarca, Adi Laurentiu and Erez, Offer and Papp, Zoltán and Romero, Roberto},
	journal-iso = {NŐGYÓGYÁSZATI ÉS SZÜLÉSZETI TOVÁBBKÉPZŐ SZEMLE},
	journal = {NŐGYÓGYÁSZATI ÉS SZÜLÉSZETI TOVÁBBKÉPZŐ SZEMLE},
	volume = {24},
	unique-id = {32725682},
	issn = {1585-8731},
	year = {2022},
	pages = {6-16},
	orcid-numbers = {Szilágyi, András/0000-0002-1773-6861}
}

@article{MTMT:32124679,
	title = {Crowdsourcing assessment of maternal blood multi-omics for predicting gestational age and preterm birth},
	url = {https://m2.mtmt.hu/api/publication/32124679},
	author = {Tarca, A.L. and Pataki, Bálint Ármin and Romero, R. and Sirota, M. and Guan, Y. and Kutum, R. and Gomez-Lopez, N. and Done, B. and Bhatti, G. and Yu, T. and Andreoletti, G. and Chaiworapongsa, T. and Hassan, S.S. and Hsu, C.-D. and Aghaeepour, N. and Stolovitzky, G. and Csabai, István and Costello, J.C.},
	doi = {10.1016/j.xcrm.2021.100323},
	journal-iso = {CELL REP MED},
	journal = {CELL REPORTS MEDICINE},
	volume = {2},
	unique-id = {32124679},
	issn = {2666-3791},
	abstract = {Identification of pregnancies at risk of preterm birth (PTB), the leading cause of newborn deaths, remains challenging given the syndromic nature of the disease. We report a longitudinal multi-omics study coupled with a DREAM challenge to develop predictive models of PTB. The findings indicate that whole-blood gene expression predicts ultrasound-based gestational ages in normal and complicated pregnancies (r = 0.83) and, using data collected before 37 weeks of gestation, also predicts the delivery date in both normal pregnancies (r = 0.86) and those with spontaneous preterm birth (r = 0.75). Based on samples collected before 33 weeks in asymptomatic women, our analysis suggests that expression changes preceding preterm prelabor rupture of the membranes are consistent across time points and cohorts and involve leukocyte-mediated immunity. Models built from plasma proteomic data predict spontaneous preterm delivery with intact membranes with higher accuracy and earlier in pregnancy than transcriptomic models (AUROC = 0.76 versus AUROC = 0.6 at 27–33 weeks of gestation). © 2021 The Author(s)},
	keywords = {machine learning; APTAMERS; spontaneous preterm birth; Predictive modeling; plasma proteomics; collaborative competition; human transcriptome arrays; preterm labor and delivery; whole blood transcriptomics},
	year = {2021},
	eissn = {2666-3791},
	orcid-numbers = {Csabai, István/0000-0001-9232-9898; Szilágyi, András/0000-0002-1773-6861}
}

@article{MTMT:31677587,
	title = {Ligand-induced conformational rearrangements regulate the switch between membrane-proximal and distal functions of Rho kinase 2.},
	url = {https://m2.mtmt.hu/api/publication/31677587},
	author = {Hajdú, István and Szilágyi, András and Végh, Barbara and Wacha, András Ferenc and Györffy, Dániel and Gráczer, Éva Laura and Somogyi, Márk and Gál, Péter and Závodszky, Péter},
	doi = {10.1038/s42003-020-01450-x},
	journal-iso = {COMMUN BIOL},
	journal = {COMMUNICATIONS BIOLOGY},
	volume = {3},
	unique-id = {31677587},
	abstract = {Rho-associated protein kinase 2 (ROCK2) is a membrane-anchored, long, flexible, multidomain, multifunctional protein. Its functions can be divided into two categories: membrane-proximal and membrane-distal. A recent study concluded that membrane-distal functions require the fully extended conformation, and this conclusion was supported by electron microscopy. The present solution small-angle X-ray scattering (SAXS) study revealed that ROCK2 population is a dynamic mixture of folded and partially extended conformers. Binding of RhoA to the coiled-coil domain shifts the equilibrium towards the partially extended state. Enzyme activity measurements suggest that the binding of natural protein substrates to the kinase domain breaks up the interaction between the N-terminal kinase and C-terminal regulatory domains, but smaller substrate analogues do not. The present study reveals the dynamic behaviour of this long, dimeric molecule in solution, and our structural model provides a mechanistic explanation for a set of membrane-proximal functions while allowing for the existence of an extended conformation in the case of membrane-distal functions.},
	year = {2020},
	eissn = {2399-3642},
	orcid-numbers = {Szilágyi, András/0000-0002-1773-6861; Végh, Barbara/0000-0002-1405-4136; Wacha, András Ferenc/0000-0002-9609-0893}
}

@article{MTMT:30625253,
	title = {New type of interaction between the SARAH domain of the tumour suppressor RASSF1A and its mitotic kinase Aurora A},
	url = {https://m2.mtmt.hu/api/publication/30625253},
	author = {Szimler, Tamás and Gráczer, Éva Laura and Györffy, Dániel and Végh, Barbara and Szilágyi, András and Hajdú, István and Závodszky, Péter and Kazinczyné Vas, Mária},
	doi = {10.1038/s41598-019-41972-x},
	journal-iso = {SCI REP},
	journal = {SCIENTIFIC REPORTS},
	volume = {9},
	unique-id = {30625253},
	issn = {2045-2322},
	year = {2019},
	eissn = {2045-2322},
	orcid-numbers = {Végh, Barbara/0000-0002-1405-4136; Szilágyi, András/0000-0002-1773-6861}
}

@article{MTMT:3168308,
	title = {Segment swapping aided the evolution of enzyme function: The case of uroporphyrinogen III synthase.},
	url = {https://m2.mtmt.hu/api/publication/3168308},
	author = {Szilágyi, András and Györffy, Dániel and Závodszky, Péter},
	doi = {10.1002/prot.25190},
	journal-iso = {PROTEINS},
	journal = {PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS},
	volume = {85},
	unique-id = {3168308},
	issn = {0887-3585},
	abstract = {In an earlier study, we showed that two-domain segment-swapped proteins can evolve by domain swapping and fusion, resulting in a protein with two linkers connecting its domains. We proposed that a potential evolutionary advantage of this topology may be the restriction of interdomain motions, which may facilitate domain closure by a hinge-like movement, crucial for the function of many enzymes. Here, we test this hypothesis computationally on uroporphyrinogen III synthase, a two-domain segment-swapped enzyme essential in porphyrin metabolism. To compare the interdomain flexibility between the wild-type, segment-swapped enzyme (having two interdomain linkers) and circular permutants of the same enzyme having only one interdomain linker, we performed geometric and molecular dynamics simulations for these species in their ligand-free and ligand-bound forms. We find that in the ligand-free form, interdomain motions in the wild-type enzyme are significantly more restricted than they would be with only one interdomain linker, while the flexibility difference is negligible in the ligand-bound form. We also estimated the entropy costs of ligand binding associated with the interdomain motions, and find that the change in domain connectivity due to segment swapping results in a reduction of this entropy cost, corresponding to approximately 20% of the total ligand binding free energy. In addition, the restriction of interdomain motions may also help the functional domain-closure motion required for catalysis. This suggests that the evolution of the segment-swapped topology facilitated the evolution of enzyme function for this protein by influencing its dynamic properties. Proteins 2016; 85:46-53. (c) 2016 Wiley Periodicals, Inc.},
	year = {2017},
	eissn = {1097-0134},
	pages = {46-53},
	orcid-numbers = {Szilágyi, András/0000-0002-1773-6861}
}