Gábor Tusnády - Academia.edu (original) (raw)

Papers by Gábor Tusnády

Genome Announcements, 2015

The draft genome sequence of a novel Mycoplasma strain, designated Mycoplasma sp. HU2014, has bee... more The draft genome sequence of a novel Mycoplasma strain, designated Mycoplasma sp. HU2014, has been determined. The genome comprises 1,084,927 nucleotides and was obtained from a mycoplasma-infected culture of chicken DT40 cells. Phylogenetic analysis places this taxon in a group comprising the closely related species Mycoplasma yeatsii and Mycoplasma cottewii.

Biology Direct, 2015

Background: Transmembrane proteins have important roles in cells, as they are involved in energy ... more Background: Transmembrane proteins have important roles in cells, as they are involved in energy production, signal transduction, cell-cell interaction, cell-cell communication and more. In human cells, they are frequently targets for pharmaceuticals; therefore, knowledge about their properties and structure is crucial. Topology of transmembrane proteins provide a low resolution structural information, which can be a starting point for either laboratory experiments or modelling their 3D structures. Results: Here, we present a database of the human α-helical transmembrane proteome, including the predicted and/or experimentally established topology of each transmembrane protein, together with the reliability of the prediction. In order to distinguish transmembrane proteins in the proteome as well as for topology prediction, we used a newly developed consensus method (CCTOP) that incorporates recent state of the art methods, with tested accuracies on a novel human benchmark protein set. CCTOP utilizes all available structure and topology data as well as bioinformatical evidences for topology prediction in a probabilistic framework provided by the hidden Markov model. This method shows the highest accuracy (98.5 % for discrinimating between transmembrane and nontransmembrane proteins and 84 % for per protein topology prediction) among the dozen tested topology prediction methods. Analysis of the human proteome with the CCTOP indicates that it contains 4998 (26 %) transmembrane proteins. Besides predicting topology, reliability of the predictions is estimated as well, and it is demonstrated that the per protein prediction accuracies of more than 60 % of the predictions are over 98 % on the benchmark sets and most probably on the predicted human transmembrane proteome too. Conclusions: Here, we present the most accurate prediction of the human transmembrane proteome together with the experimental topology data. These data, as well as various statistics about the human transmembrane proteins and their topologies can be downloaded from and can be visualized at the website of the human transmembrane proteome

Proceedings. 2001 IEEE International Symposium on Information Theory (IEEE Cat. No.01CH37252), 2001

Motivated by problems in robust statistics we first give a simple proof of the following: Given a... more Motivated by problems in robust statistics we first give a simple proof of the following: Given a probability measure P and positive measures µ < ν, the γ−divergence from P of probability measures Q satisfying µ ≤ Q or µ ≤ Q ≤ ν is minimized by an explicitly determined Q * not depending on (the convex function) γ. Next we address γ−divergence minimization under the above inequality constraint and additional moment constraints.

BMC bioinformatics, 2006

A large number of PCR primer-design softwares are available online. However, only very few of the... more A large number of PCR primer-design softwares are available online. However, only very few of them can be used for the design of primers to amplify bisulfite-treated DNA templates, necessary to determine genomic DNA methylation profiles. Indeed, the number of studies on bisulfite-treated templates exponentially increases as determining DNA methylation becomes more important in the diagnosis of cancers. Bisulfite-treated DNA is difficult to amplify since undesired PCR products are often amplified due to the increased sequence redundancy after the chemical conversion. In order to increase the efficiency of PCR primer-design, we have developed BiSearch web server, an online primer-design tool for both bisulfite-treated and native DNA templates. The web tool is composed of a primer-design and an electronic PCR (ePCR) algorithm. The completely reformulated ePCR module detects potential mispriming sites as well as undesired PCR products on both cDNA and native or bisulfite-treated genomic...

FEBS letters, Jan 13, 2006

In this review, we summarize the currently available information on the membrane topology of some... more In this review, we summarize the currently available information on the membrane topology of some key members of the human ABC protein subfamilies, and present the predicted domain arrangements. In the lack of high-resolution structures for eukaryotic ABC transporters this topology is based only on prediction algorithms and biochemical data for the location of various segments of the polypeptide chain, relative to the membrane. We suggest that topology models generated by the available prediction methods should only be used as guidelines to provide a basis of experimental strategies for the elucidation of the membrane topology.

Nucleic acids research, 2005

Bisulfite genomic sequencing is the most widely used technique to analyze the 5-methylation of cy... more Bisulfite genomic sequencing is the most widely used technique to analyze the 5-methylation of cytosines, the prevalent covalent DNA modification in mammals. The process is based on the selective transformation of unmethylated cytosines to uridines. Then, the investigated genomic regions are PCR amplified, subcloned and sequenced. During sequencing, the initially unmethylated cytosines are detected as thymines. The efficacy of bisulfite PCR is generally low; mispriming and non-specific amplification often occurs due to the T richness of the target sequences. In order to ameliorate the efficiency of PCR, we developed a new primer-design software called BiSearch, available on the World Wide Web. It has the unique property of analyzing the primer pairs for mispriming sites on the bisulfite-treated genome and determines potential non-specific amplification products with a new search algorithm. The options of primer-design and analysis for mispriming sites can be used sequentially or sep...

Nucleic acids research, 2005

PDB_TM is a database for transmembrane proteins with known structures. It aims to collect all tra... more PDB_TM is a database for transmembrane proteins with known structures. It aims to collect all transmembrane proteins that are deposited in the protein structure database (PDB) and to determine their membrane-spanning regions. These assignments are based on the TMDET algorithm, which uses only structural information to locate the most likely position of the lipid bilayer and to distinguish between transmembrane and globular proteins. This algorithm was applied to all PDB entries and the results were collected in the PDB_TM database. By using TMDET algorithm, the PDB_TM database can be automatically updated every week, keeping it synchronized with the latest PDB updates. The PDB_TM database is available at http://www.enzim.hu/PDB_TM.

Journal of cell science, 2000

The human multidrug resistance protein (MRP1) contributes to drug resistance in cancer cells. In ... more The human multidrug resistance protein (MRP1) contributes to drug resistance in cancer cells. In addition to an MDR1-like core, MRP1 contains an N-terminal membrane-bound (TMD(0)) region and a cytoplasmic linker (L(0)), both characteristic of several members of the MRP family. In order to study the role of the TMD(0) and L(0) regions, we constructed various truncated and mutated MRP1, and chimeric MRP1-MDR1 molecules, which were expressed in insect (Sf9) and polarized mammalian (MDCKII) cells. The function of the various proteins was examined in isolated membrane vesicles by measuring the transport of leukotriene C(4) and other glutathione conjugates, and by vanadate-dependent nucleotide occlusion. Cellular localization, and glutathione-conjugate and drug transport, were also studied in MDCKII cells. We found that chimeric proteins consisting of N-terminal fragments of MRP1 fused to the N terminus of MDR1 preserved the transport, nucleotide occlusion and apical membrane routing of w...

In this review, we summarize the currently available information on the membrane topology of some... more In this review, we summarize the currently available information on the membrane topology of some key members of the human ABC protein subfamilies, and present the predicted domain arrangements. In the lack of high-resolution structures for eukaryotic ABC transporters this topology is based only on prediction algorithms and biochemical data for the location of various segments of the polypeptide chain, relative to the mem- brane. We suggest that topology models generated by the avail- able prediction methods should only be used as guidelines to provide a basis of experimental strategies for the elucidation of the membrane topology. 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

ABSTRACT Vizsgáltunk Wiener folyamatokat és független valószínűségi változók összegét. Eredmények... more ABSTRACT Vizsgáltunk Wiener folyamatokat és független valószínűségi változók összegét. Eredményeket értünk el a 3 és magasabb dimenziós Wiener folyamat lokális idejének a tanulmányozásában és áltálanosítottuk Erdős és Taylor, Pólya, Erdős és Darling eredményeit. Bebizonyitottunk néhány a pénzügyi matematika által motivált statisztikai eredményt. E problemák vizsgálata néhány Hilbert tér értékű valószínűségi változókról szóló nem triviális feladat megoldását is követelte. Néhány számelmélettel is kapcsolatos sztochasztikus problémát is vizsgáltunk, ahol az eredmény bizonyos véletlen jelenségeken kívül egy számsorozat diophantikus tulajdonságain is múlott. Ily módon néhány Kac egy klasszikus problémájához kapcsolódó új eredményt is kaptunk. Bebizonyítottunk néhány éles becslést U-statisztikákról és független valószínűségi változók más nem lineáris funkcionáljairól. Az ilyen eredményeknek érdekes statisztikai alkalmazásai is vannak. Foglalkoztunk a véletlen permutációk elméletével. Bebizonyítottuk P. McCullagh egy sejtését és érdekes algebrai statisztikai eredményeket kaptunk Diaconis egy klasszikus példáját vizsgálva. Továbbá biostatisztikai motivációjú vizsgálatokat is folytattunk. Továbbfejlesztettük Kauffman Boole network-ökről szóló modelljét és nehány immunológiai és népesség statisztikai vizsgálatot folytattunk. | We investigated Wiener processes and sums of independent random variables. We studied the local time of 3 and higher dimensional Wiener process, and generalized some classical results of Erdos and Taylor, Polya, Erdos and Darling etc. We also studied some new type of statistical problems partly motivated by financial mathematics. These problems demanded the study of some non-trivial problems about random variables taking their values in a Hilbert space. We also studied some problems related to number theory, where the behaviour of some sequences depended both on some random phenomena and diophantic behaviour of some sequences. We got in such a way some new results about a classical problem of Mark Kac. We also got some new sharp estimates about U-statistics and other non-linear functionals of independent random variables. Such results may have interesting statistical applications. We also studied the theory of random permutations. We have proved a conjecture of P. McCullagh and obtained some interesting result on algebraic statistic motivated by a classical example of Diaconis. We also had some other investigations motivated by biostatistics. We developped the model of Kauffman about Boole networks and studied some problems of immunology and population genetics.

The cerebral cortex is probably the most prominent example of natural information processing netw... more The cerebral cortex is probably the most prominent example of natural information processing networks. It is therefore of major importance how this network is organised. At the lowest level the cortical network is composed by physically (i.e. via chemical and electrical synapses) connected nerve cells. At a higher organizational level, the cortex consists of a set of structurally and functionally specialised regions or areas with highly variable shape and size . Since the use of sensitive and powerful tract tracing techniques is not feasible in humans, the neuronal connections between the areas have been being studied intensely in non-human primates, especially in the macaque, which serves as a model of the human cortex . Kötter and Stephan pointed out the importance of the consideration of "missing data" -connections that have never been checked experimentally, therefore possibly erroneously being treated as missing. An accurate network model should take into account that a disconnected pair of vertices can represent either a pair of areas that are known to be disconnected, or a pair of areas whose connectivity has not been checked yet. Because it is reasonable to assume that a considerable part of the large-scale cortical network is still unknown, it is an important problem to predict the location of additional connections that have not been charted yet. The two studies published up to now present data on such predictions of yet unknown connections in the cortex [1, 2]. However, they also report a relatively large number of violations, where known existent connections were predicted as non-existent and known non-existent connections to be existent in the reconstructed graphs. This suggests that using other approaches could result in better reconstruction of the cortical network. The aim of the present study was therefore to find a reconstruction algorithm that predicts unknown edges in an arbitrary network under some very general assumptions that do not rely on domain-specific a priori knowledge.

Ebben a pályázatban a FEBS Letters felkérésére összefoglalót készítettünk a humán ABC fehérjék me... more Ebben a pályázatban a FEBS Letters felkérésére összefoglalót készítettünk a humán ABC fehérjék membrán topológiájáról, továbbfejlesztettük a BiSearch PCR primer-tervező szoftvert (http://bisearch.enzim.hu), amelyről a BMC Bioinformatics-ban számoltunk be. Felkérésre írtunk egy összefoglaló könyvfejezetet is erről a témáról, ami a Methods in Molecular Biology-ban jelent meg. Létrehoztunk továbbá két topológiai adatokat tartalmazó adatbázist, amelyeket TOPDB (http://topdb.enzim.hu) és TOPDOM (http://topdom.enzim.hu) adatbázisnak neveztünk el. A TOPDB adatbázis az ismert szerkezetű transzmembrán fehérjék topológiai adatait, valamint az irodalomban található különböző fizikai-kémiai, molekuláris biológiai módszerrel nyert topológiai adatokat tartalmazza. A TOPDOM adatbázis olyan domén és szekvencia motívum adatokat tartalmaz, amelyek a transzmembrán fehérjékben konzervatív módon találhatóak meg. Ezeket a munkákat a Nucleic Acids Research, illetve a Bioinformatics folyóiratban közöltük. ...

Megállapítottuk, hogy az ABCC6 gén duplikációi a low-copy repeat 16a elemekhez kötődnek, és ilyen... more Megállapítottuk, hogy az ABCC6 gén duplikációi a low-copy repeat 16a elemekhez kötődnek, és ilyen duplikációk több alkalommal is bekövetkeztek különböző főemlős fajokban. Populációgenetikai vizsgálatunkban kimutattuk, hogy egy inaktív ABCC6 allél növeli a koronáriás artéria betegség (CAD) kialakulásának esélyét. Az ABCC6 expressziójánk szabályozását is vizsgáltuk, megállapítottuk, hogy az ERK1/2 szignál-útvonal és a HNF4 transzkripciós faktor felelős az ABCC6 szövet-specifikus szabályozásáért. Megalkottuk az ABCC6 transzporter homológia modelljét, és tanulmányoztuk az ismert 119 misszensz PXE-t okozó mutáció eloszlását. A komplex domén-domén határfelületeken a misszensz mutációk jelentős feldúsúlását figyeltük meg, ami ezen kapcsolatok fontosságának genetikai bizonyítéka. Az ABCC6 viszgálatára alkalmas új állat modellt fejlesztettünk ki: a zebrahal (Danio rerio) modell-rendszert. Bemutattuk, hogy az ecetmuslica MRP az ortológ humán ABCC fehérjékhez hasonló biokémiai tulajdonságokkal...

Kidolgoztunk egy eljárást, a TMDET-et, amivel meghatározható a fehérjék elhelyezkedése és orientá... more Kidolgoztunk egy eljárást, a TMDET-et, amivel meghatározható a fehérjék elhelyezkedése és orientációja a membránhoz képest (http://tmdet.enzim.hu/). A TMDET felhasználásával elkészitettük az ismert térszerkezetű transzmembrán fehérjék adatbázisát a PDB_TM-et (http://pdbtm.enzim.hu/). Készitettünk továbbá egy transzmembrán fehérje topológiai adatbázist a TOPDB-t (http://topdb.enzim.hu/). Az adatbázisokhoz kereső és elemző programokat is készitettünk. Korábban kifejlesztett topologia becslő algoritmusainkkal valamint a fenti szerverekkel összeállitást készitettünk a humán ABC transzporter fehérjékről. A kizárólag transzmembrán fehérjéket érintő módszerek mellett ki kellett dolgozni, általános minden fehérjét érintőket eljárásokai is. IUPred néven algoritmust dolgoztunk ki fehérjék rendezetlen szegmenseinek becslésére (http://iupred.enzim.hu/). Meghatároztuk, hogyan változott a rendezetlenség mértéke a törzsfejlődés során, milyen szerepet játszanak ezek a rendezetlen szakaszok a fehérj...

Nucleic Acids Research, 2014

The Topology Data Bank of Transmembrane Proteins (TOPDB, http://topdb.enzim.ttk.mta.hu) contains ... more The Topology Data Bank of Transmembrane Proteins (TOPDB, http://topdb.enzim.ttk.mta.hu) contains experimentally determined topology data of transmembrane proteins. Recently, we have updated TOPDB from several sources and utilized a newly developed topology prediction algorithm to determine the most reliable topology using the results of experiments as constraints. In addition to collecting the experimentally determined topology data published in the last couple of years, we gathered topographies defined by the TMDET algorithm using 3D structures from the PDBTM. Results of global topology analysis of various organisms as well as topology data generated by high throughput techniques, like the sequential positions of N- or O-glycosylations were incorporated into the TOPDB database. Moreover, a new algorithm was developed to integrate scattered topology data from various publicly available databases and a new method was introduced to measure the reliability of predicted topologies. We show that reliability values highly correlate with the per protein topology accuracy of the utilized prediction method. Altogether, more than 52,000 new topology data and more than 2600 new transmembrane proteins have been collected since the last public release of the TOPDB database.

International Journal of Biometeorology, 2014

Weather classification approaches may be useful tools in modelling the occurrence of respiratory ... more Weather classification approaches may be useful tools in modelling the occurrence of respiratory diseases. The aim of the study is to compare the performance of an objectively defined weather classification and the Spatial Synoptic Classification (SSC) in classifying emergency department (ED) visits for acute asthma depending from weather, air pollutants, and airborne pollen variables for Szeged, Hungary, for the 9-year period 1999-2007. The research is performed for three different pollen-related periods of the year and the annual data set. According to age and gender, nine patient categories, eight meteorological variables, seven chemical air pollutants, and two pollen categories were used. In general, partly dry and cold air and partly warm and humid air aggravate substantially the symptoms of asthmatics. Our major findings are consistent with this establishment. Namely, for the objectively defined weather types favourable conditions for asthma ER visits occur when an anticyclonic ridge weather situation happens with near extreme temperature and humidity parameters. Accordingly, the SSC weather types facilitate aggravating asthmatic conditions if warm or cool weather occur with high humidity in both cases. Favourable conditions for asthma attacks are confirmed in the extreme seasons when atmospheric stability contributes to enrichment of air pollutants. The total efficiency of the two classification approaches is similar in spite of the fact that the methodology for derivation of the individual types within the two classification approaches is completely different.

Methods and Algorithms, 2010

Structural Bioinformatics of Membrane Proteins, 2010

ABSTRACT Transmembrane proteins are involved in a wide variety of vital biological processes incl... more ABSTRACT Transmembrane proteins are involved in a wide variety of vital biological processes including transport of water-soluble molecules, flow of information and energy production. Despite significant efforts to determine the structures of these proteins, only a few thousand solved structures are known so far. Here, we review the various resources for structure-related information on these types of proteins ranging from the D structure to the topology and from the up-to-date databases to the various Internet sites and servers dealing with structure prediction and structure analysis. Abbreviations: 3D, three dimensional; PDB, Protein Data Bank; TMP, transmembrane protein.

Genome Announcements, 2015

The draft genome sequence of a novel Mycoplasma strain, designated Mycoplasma sp. HU2014, has bee... more The draft genome sequence of a novel Mycoplasma strain, designated Mycoplasma sp. HU2014, has been determined. The genome comprises 1,084,927 nucleotides and was obtained from a mycoplasma-infected culture of chicken DT40 cells. Phylogenetic analysis places this taxon in a group comprising the closely related species Mycoplasma yeatsii and Mycoplasma cottewii.

Biology Direct, 2015

Background: Transmembrane proteins have important roles in cells, as they are involved in energy ... more Background: Transmembrane proteins have important roles in cells, as they are involved in energy production, signal transduction, cell-cell interaction, cell-cell communication and more. In human cells, they are frequently targets for pharmaceuticals; therefore, knowledge about their properties and structure is crucial. Topology of transmembrane proteins provide a low resolution structural information, which can be a starting point for either laboratory experiments or modelling their 3D structures. Results: Here, we present a database of the human α-helical transmembrane proteome, including the predicted and/or experimentally established topology of each transmembrane protein, together with the reliability of the prediction. In order to distinguish transmembrane proteins in the proteome as well as for topology prediction, we used a newly developed consensus method (CCTOP) that incorporates recent state of the art methods, with tested accuracies on a novel human benchmark protein set. CCTOP utilizes all available structure and topology data as well as bioinformatical evidences for topology prediction in a probabilistic framework provided by the hidden Markov model. This method shows the highest accuracy (98.5 % for discrinimating between transmembrane and nontransmembrane proteins and 84 % for per protein topology prediction) among the dozen tested topology prediction methods. Analysis of the human proteome with the CCTOP indicates that it contains 4998 (26 %) transmembrane proteins. Besides predicting topology, reliability of the predictions is estimated as well, and it is demonstrated that the per protein prediction accuracies of more than 60 % of the predictions are over 98 % on the benchmark sets and most probably on the predicted human transmembrane proteome too. Conclusions: Here, we present the most accurate prediction of the human transmembrane proteome together with the experimental topology data. These data, as well as various statistics about the human transmembrane proteins and their topologies can be downloaded from and can be visualized at the website of the human transmembrane proteome

Proceedings. 2001 IEEE International Symposium on Information Theory (IEEE Cat. No.01CH37252), 2001

Motivated by problems in robust statistics we first give a simple proof of the following: Given a... more Motivated by problems in robust statistics we first give a simple proof of the following: Given a probability measure P and positive measures µ < ν, the γ−divergence from P of probability measures Q satisfying µ ≤ Q or µ ≤ Q ≤ ν is minimized by an explicitly determined Q * not depending on (the convex function) γ. Next we address γ−divergence minimization under the above inequality constraint and additional moment constraints.

BMC bioinformatics, 2006

A large number of PCR primer-design softwares are available online. However, only very few of the... more A large number of PCR primer-design softwares are available online. However, only very few of them can be used for the design of primers to amplify bisulfite-treated DNA templates, necessary to determine genomic DNA methylation profiles. Indeed, the number of studies on bisulfite-treated templates exponentially increases as determining DNA methylation becomes more important in the diagnosis of cancers. Bisulfite-treated DNA is difficult to amplify since undesired PCR products are often amplified due to the increased sequence redundancy after the chemical conversion. In order to increase the efficiency of PCR primer-design, we have developed BiSearch web server, an online primer-design tool for both bisulfite-treated and native DNA templates. The web tool is composed of a primer-design and an electronic PCR (ePCR) algorithm. The completely reformulated ePCR module detects potential mispriming sites as well as undesired PCR products on both cDNA and native or bisulfite-treated genomic...

FEBS letters, Jan 13, 2006

In this review, we summarize the currently available information on the membrane topology of some... more In this review, we summarize the currently available information on the membrane topology of some key members of the human ABC protein subfamilies, and present the predicted domain arrangements. In the lack of high-resolution structures for eukaryotic ABC transporters this topology is based only on prediction algorithms and biochemical data for the location of various segments of the polypeptide chain, relative to the membrane. We suggest that topology models generated by the available prediction methods should only be used as guidelines to provide a basis of experimental strategies for the elucidation of the membrane topology.

Nucleic acids research, 2005

Bisulfite genomic sequencing is the most widely used technique to analyze the 5-methylation of cy... more Bisulfite genomic sequencing is the most widely used technique to analyze the 5-methylation of cytosines, the prevalent covalent DNA modification in mammals. The process is based on the selective transformation of unmethylated cytosines to uridines. Then, the investigated genomic regions are PCR amplified, subcloned and sequenced. During sequencing, the initially unmethylated cytosines are detected as thymines. The efficacy of bisulfite PCR is generally low; mispriming and non-specific amplification often occurs due to the T richness of the target sequences. In order to ameliorate the efficiency of PCR, we developed a new primer-design software called BiSearch, available on the World Wide Web. It has the unique property of analyzing the primer pairs for mispriming sites on the bisulfite-treated genome and determines potential non-specific amplification products with a new search algorithm. The options of primer-design and analysis for mispriming sites can be used sequentially or sep...

Nucleic acids research, 2005

PDB_TM is a database for transmembrane proteins with known structures. It aims to collect all tra... more PDB_TM is a database for transmembrane proteins with known structures. It aims to collect all transmembrane proteins that are deposited in the protein structure database (PDB) and to determine their membrane-spanning regions. These assignments are based on the TMDET algorithm, which uses only structural information to locate the most likely position of the lipid bilayer and to distinguish between transmembrane and globular proteins. This algorithm was applied to all PDB entries and the results were collected in the PDB_TM database. By using TMDET algorithm, the PDB_TM database can be automatically updated every week, keeping it synchronized with the latest PDB updates. The PDB_TM database is available at http://www.enzim.hu/PDB_TM.

Journal of cell science, 2000

The human multidrug resistance protein (MRP1) contributes to drug resistance in cancer cells. In ... more The human multidrug resistance protein (MRP1) contributes to drug resistance in cancer cells. In addition to an MDR1-like core, MRP1 contains an N-terminal membrane-bound (TMD(0)) region and a cytoplasmic linker (L(0)), both characteristic of several members of the MRP family. In order to study the role of the TMD(0) and L(0) regions, we constructed various truncated and mutated MRP1, and chimeric MRP1-MDR1 molecules, which were expressed in insect (Sf9) and polarized mammalian (MDCKII) cells. The function of the various proteins was examined in isolated membrane vesicles by measuring the transport of leukotriene C(4) and other glutathione conjugates, and by vanadate-dependent nucleotide occlusion. Cellular localization, and glutathione-conjugate and drug transport, were also studied in MDCKII cells. We found that chimeric proteins consisting of N-terminal fragments of MRP1 fused to the N terminus of MDR1 preserved the transport, nucleotide occlusion and apical membrane routing of w...

In this review, we summarize the currently available information on the membrane topology of some... more In this review, we summarize the currently available information on the membrane topology of some key members of the human ABC protein subfamilies, and present the predicted domain arrangements. In the lack of high-resolution structures for eukaryotic ABC transporters this topology is based only on prediction algorithms and biochemical data for the location of various segments of the polypeptide chain, relative to the mem- brane. We suggest that topology models generated by the avail- able prediction methods should only be used as guidelines to provide a basis of experimental strategies for the elucidation of the membrane topology. 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

ABSTRACT Vizsgáltunk Wiener folyamatokat és független valószínűségi változók összegét. Eredmények... more ABSTRACT Vizsgáltunk Wiener folyamatokat és független valószínűségi változók összegét. Eredményeket értünk el a 3 és magasabb dimenziós Wiener folyamat lokális idejének a tanulmányozásában és áltálanosítottuk Erdős és Taylor, Pólya, Erdős és Darling eredményeit. Bebizonyitottunk néhány a pénzügyi matematika által motivált statisztikai eredményt. E problemák vizsgálata néhány Hilbert tér értékű valószínűségi változókról szóló nem triviális feladat megoldását is követelte. Néhány számelmélettel is kapcsolatos sztochasztikus problémát is vizsgáltunk, ahol az eredmény bizonyos véletlen jelenségeken kívül egy számsorozat diophantikus tulajdonságain is múlott. Ily módon néhány Kac egy klasszikus problémájához kapcsolódó új eredményt is kaptunk. Bebizonyítottunk néhány éles becslést U-statisztikákról és független valószínűségi változók más nem lineáris funkcionáljairól. Az ilyen eredményeknek érdekes statisztikai alkalmazásai is vannak. Foglalkoztunk a véletlen permutációk elméletével. Bebizonyítottuk P. McCullagh egy sejtését és érdekes algebrai statisztikai eredményeket kaptunk Diaconis egy klasszikus példáját vizsgálva. Továbbá biostatisztikai motivációjú vizsgálatokat is folytattunk. Továbbfejlesztettük Kauffman Boole network-ökről szóló modelljét és nehány immunológiai és népesség statisztikai vizsgálatot folytattunk. | We investigated Wiener processes and sums of independent random variables. We studied the local time of 3 and higher dimensional Wiener process, and generalized some classical results of Erdos and Taylor, Polya, Erdos and Darling etc. We also studied some new type of statistical problems partly motivated by financial mathematics. These problems demanded the study of some non-trivial problems about random variables taking their values in a Hilbert space. We also studied some problems related to number theory, where the behaviour of some sequences depended both on some random phenomena and diophantic behaviour of some sequences. We got in such a way some new results about a classical problem of Mark Kac. We also got some new sharp estimates about U-statistics and other non-linear functionals of independent random variables. Such results may have interesting statistical applications. We also studied the theory of random permutations. We have proved a conjecture of P. McCullagh and obtained some interesting result on algebraic statistic motivated by a classical example of Diaconis. We also had some other investigations motivated by biostatistics. We developped the model of Kauffman about Boole networks and studied some problems of immunology and population genetics.

The cerebral cortex is probably the most prominent example of natural information processing netw... more The cerebral cortex is probably the most prominent example of natural information processing networks. It is therefore of major importance how this network is organised. At the lowest level the cortical network is composed by physically (i.e. via chemical and electrical synapses) connected nerve cells. At a higher organizational level, the cortex consists of a set of structurally and functionally specialised regions or areas with highly variable shape and size . Since the use of sensitive and powerful tract tracing techniques is not feasible in humans, the neuronal connections between the areas have been being studied intensely in non-human primates, especially in the macaque, which serves as a model of the human cortex . Kötter and Stephan pointed out the importance of the consideration of "missing data" -connections that have never been checked experimentally, therefore possibly erroneously being treated as missing. An accurate network model should take into account that a disconnected pair of vertices can represent either a pair of areas that are known to be disconnected, or a pair of areas whose connectivity has not been checked yet. Because it is reasonable to assume that a considerable part of the large-scale cortical network is still unknown, it is an important problem to predict the location of additional connections that have not been charted yet. The two studies published up to now present data on such predictions of yet unknown connections in the cortex [1, 2]. However, they also report a relatively large number of violations, where known existent connections were predicted as non-existent and known non-existent connections to be existent in the reconstructed graphs. This suggests that using other approaches could result in better reconstruction of the cortical network. The aim of the present study was therefore to find a reconstruction algorithm that predicts unknown edges in an arbitrary network under some very general assumptions that do not rely on domain-specific a priori knowledge.

Ebben a pályázatban a FEBS Letters felkérésére összefoglalót készítettünk a humán ABC fehérjék me... more Ebben a pályázatban a FEBS Letters felkérésére összefoglalót készítettünk a humán ABC fehérjék membrán topológiájáról, továbbfejlesztettük a BiSearch PCR primer-tervező szoftvert (http://bisearch.enzim.hu), amelyről a BMC Bioinformatics-ban számoltunk be. Felkérésre írtunk egy összefoglaló könyvfejezetet is erről a témáról, ami a Methods in Molecular Biology-ban jelent meg. Létrehoztunk továbbá két topológiai adatokat tartalmazó adatbázist, amelyeket TOPDB (http://topdb.enzim.hu) és TOPDOM (http://topdom.enzim.hu) adatbázisnak neveztünk el. A TOPDB adatbázis az ismert szerkezetű transzmembrán fehérjék topológiai adatait, valamint az irodalomban található különböző fizikai-kémiai, molekuláris biológiai módszerrel nyert topológiai adatokat tartalmazza. A TOPDOM adatbázis olyan domén és szekvencia motívum adatokat tartalmaz, amelyek a transzmembrán fehérjékben konzervatív módon találhatóak meg. Ezeket a munkákat a Nucleic Acids Research, illetve a Bioinformatics folyóiratban közöltük. ...

Megállapítottuk, hogy az ABCC6 gén duplikációi a low-copy repeat 16a elemekhez kötődnek, és ilyen... more Megállapítottuk, hogy az ABCC6 gén duplikációi a low-copy repeat 16a elemekhez kötődnek, és ilyen duplikációk több alkalommal is bekövetkeztek különböző főemlős fajokban. Populációgenetikai vizsgálatunkban kimutattuk, hogy egy inaktív ABCC6 allél növeli a koronáriás artéria betegség (CAD) kialakulásának esélyét. Az ABCC6 expressziójánk szabályozását is vizsgáltuk, megállapítottuk, hogy az ERK1/2 szignál-útvonal és a HNF4 transzkripciós faktor felelős az ABCC6 szövet-specifikus szabályozásáért. Megalkottuk az ABCC6 transzporter homológia modelljét, és tanulmányoztuk az ismert 119 misszensz PXE-t okozó mutáció eloszlását. A komplex domén-domén határfelületeken a misszensz mutációk jelentős feldúsúlását figyeltük meg, ami ezen kapcsolatok fontosságának genetikai bizonyítéka. Az ABCC6 viszgálatára alkalmas új állat modellt fejlesztettünk ki: a zebrahal (Danio rerio) modell-rendszert. Bemutattuk, hogy az ecetmuslica MRP az ortológ humán ABCC fehérjékhez hasonló biokémiai tulajdonságokkal...

Kidolgoztunk egy eljárást, a TMDET-et, amivel meghatározható a fehérjék elhelyezkedése és orientá... more Kidolgoztunk egy eljárást, a TMDET-et, amivel meghatározható a fehérjék elhelyezkedése és orientációja a membránhoz képest (http://tmdet.enzim.hu/). A TMDET felhasználásával elkészitettük az ismert térszerkezetű transzmembrán fehérjék adatbázisát a PDB_TM-et (http://pdbtm.enzim.hu/). Készitettünk továbbá egy transzmembrán fehérje topológiai adatbázist a TOPDB-t (http://topdb.enzim.hu/). Az adatbázisokhoz kereső és elemző programokat is készitettünk. Korábban kifejlesztett topologia becslő algoritmusainkkal valamint a fenti szerverekkel összeállitást készitettünk a humán ABC transzporter fehérjékről. A kizárólag transzmembrán fehérjéket érintő módszerek mellett ki kellett dolgozni, általános minden fehérjét érintőket eljárásokai is. IUPred néven algoritmust dolgoztunk ki fehérjék rendezetlen szegmenseinek becslésére (http://iupred.enzim.hu/). Meghatároztuk, hogyan változott a rendezetlenség mértéke a törzsfejlődés során, milyen szerepet játszanak ezek a rendezetlen szakaszok a fehérj...

Nucleic Acids Research, 2014

The Topology Data Bank of Transmembrane Proteins (TOPDB, http://topdb.enzim.ttk.mta.hu) contains ... more The Topology Data Bank of Transmembrane Proteins (TOPDB, http://topdb.enzim.ttk.mta.hu) contains experimentally determined topology data of transmembrane proteins. Recently, we have updated TOPDB from several sources and utilized a newly developed topology prediction algorithm to determine the most reliable topology using the results of experiments as constraints. In addition to collecting the experimentally determined topology data published in the last couple of years, we gathered topographies defined by the TMDET algorithm using 3D structures from the PDBTM. Results of global topology analysis of various organisms as well as topology data generated by high throughput techniques, like the sequential positions of N- or O-glycosylations were incorporated into the TOPDB database. Moreover, a new algorithm was developed to integrate scattered topology data from various publicly available databases and a new method was introduced to measure the reliability of predicted topologies. We show that reliability values highly correlate with the per protein topology accuracy of the utilized prediction method. Altogether, more than 52,000 new topology data and more than 2600 new transmembrane proteins have been collected since the last public release of the TOPDB database.

International Journal of Biometeorology, 2014

Weather classification approaches may be useful tools in modelling the occurrence of respiratory ... more Weather classification approaches may be useful tools in modelling the occurrence of respiratory diseases. The aim of the study is to compare the performance of an objectively defined weather classification and the Spatial Synoptic Classification (SSC) in classifying emergency department (ED) visits for acute asthma depending from weather, air pollutants, and airborne pollen variables for Szeged, Hungary, for the 9-year period 1999-2007. The research is performed for three different pollen-related periods of the year and the annual data set. According to age and gender, nine patient categories, eight meteorological variables, seven chemical air pollutants, and two pollen categories were used. In general, partly dry and cold air and partly warm and humid air aggravate substantially the symptoms of asthmatics. Our major findings are consistent with this establishment. Namely, for the objectively defined weather types favourable conditions for asthma ER visits occur when an anticyclonic ridge weather situation happens with near extreme temperature and humidity parameters. Accordingly, the SSC weather types facilitate aggravating asthmatic conditions if warm or cool weather occur with high humidity in both cases. Favourable conditions for asthma attacks are confirmed in the extreme seasons when atmospheric stability contributes to enrichment of air pollutants. The total efficiency of the two classification approaches is similar in spite of the fact that the methodology for derivation of the individual types within the two classification approaches is completely different.

Methods and Algorithms, 2010

Structural Bioinformatics of Membrane Proteins, 2010

ABSTRACT Transmembrane proteins are involved in a wide variety of vital biological processes incl... more ABSTRACT Transmembrane proteins are involved in a wide variety of vital biological processes including transport of water-soluble molecules, flow of information and energy production. Despite significant efforts to determine the structures of these proteins, only a few thousand solved structures are known so far. Here, we review the various resources for structure-related information on these types of proteins ranging from the D structure to the topology and from the up-to-date databases to the various Internet sites and servers dealing with structure prediction and structure analysis. Abbreviations: 3D, three dimensional; PDB, Protein Data Bank; TMP, transmembrane protein.