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See detailStars and symbiosis: microRNA- and microRNA*-mediated transcript cleavage involved in arbuscular mycorrhizal symbiosis.
Devers, Emanuel A.; Branscheid, Anja; May, Patrick UL et al

in Plant Physiology (2011), 156(4), 1990-2010

The majority of plants are able to form the arbuscular mycorrhizal (AM) symbiosis in association with AM fungi. During symbiosis development, plant cells undergo a complex reprogramming resulting in ... [more ▼]

The majority of plants are able to form the arbuscular mycorrhizal (AM) symbiosis in association with AM fungi. During symbiosis development, plant cells undergo a complex reprogramming resulting in profound morphological and physiological changes. MicroRNAs (miRNAs) are important components of the regulatory network of plant cells. To unravel the impact of miRNAs and miRNA-mediated mRNA cleavage on root cell reprogramming during AM symbiosis, we carried out high-throughput (Illumina) sequencing of small RNAs and degradome tags of Medicago truncatula roots. This led to the annotation of 243 novel miRNAs. An increased accumulation of several novel and conserved miRNAs in mycorrhizal roots suggest a role of these miRNAs during AM symbiosis. The degradome analysis led to the identification of 185 root transcripts as mature miRNA and also miRNA*-mediated mRNA cleavage targets. Several of the identified miRNA targets are known to be involved in root symbioses. In summary, the increased accumulation of specific miRNAs and the miRNA-mediated cleavage of symbiosis-relevant genes indicate that miRNAs are an important part of the regulatory network leading to symbiosis development. [less ▲]

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See detailExpression pattern suggests a role of MiR399 in the regulation of the cellular response to local Pi increase during arbuscular mycorrhizal symbiosis.
Branscheid, Anja; Sieh, Daniela; Pant, Bikram Datt et al

in Molecular Plant-Microbe Interactions (2010), 23(7), 915-26

Many plants improve their phosphate (Pi) availability by forming mutualistic associations with arbuscular mycorrhizal (AM) fungi. Pi-repleted plants are much less colonized by AM fungi than Pi-depleted ... [more ▼]

Many plants improve their phosphate (Pi) availability by forming mutualistic associations with arbuscular mycorrhizal (AM) fungi. Pi-repleted plants are much less colonized by AM fungi than Pi-depleted plants. This indicates a link between plant Pi signaling and AM development. MicroRNAs (miR) of the 399 family are systemic Pi-starvation signals important for maintenance of Pi homeostasis in Arabidopsis thaliana and might also qualify as signals regulating AM development in response to Pi availability. MiR399 could either represent the systemic low-Pi signal promoting or required for AM formation or they could act as counter players of systemic Pi-availability signals that suppress AM symbiosis. To test either of these assumptions, we analyzed the miR399 family in the AM-capable plant model Medicago truncatula and could experimentally confirm 10 novel MIR399 genes in this species. Pi-depleted plants showed increased expression of mature miR399 and multiple pri-miR399, and unexpectedly, levels of five of the 15 pri-miR399 species were higher in leaves of mycorrhizal plants than in leaves of nonmycorrhizal plants. Compared with nonmycorrhizal Pi-depleted roots, mycorrhizal roots of Pi-depleted M. truncatula and tobacco plants had increased Pi contents due to symbiotic Pi uptake but displayed higher mature miR399 levels. Expression levels of MtPho2 remained low and PHO2-dependent Pi-stress marker transcript levels remained high in these mycorrhizal roots. Hence, an AM symbiosis-related signal appears to increase miR399 expression and decrease PHO2 activity. MiR399 overexpression in tobacco suggested that miR399 alone is not sufficient to improve mycorrhizal colonization supporting the assumption that, in mycorrhizal roots, increased miR399 are necessary to keep the MtPho2 expression and activity low, which would otherwise increase in response to symbiotic Pi uptake. [less ▲]

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See detailPTGL: a database for secondary structure-based protein topologies.
May, Patrick UL; Kreuchwig, Annika; Steinke, Thomas et al

in Nucleic Acids Research (2010), 38(Database issue), 326-30

With growing amount of experimental data, the number of known protein structures also increases continuously. Classification of protein structures helps to understand relationships between protein ... [more ▼]

With growing amount of experimental data, the number of known protein structures also increases continuously. Classification of protein structures helps to understand relationships between protein structure and function. The main classification methods based on secondary structures are SCOP, CATH and TOPS, which all classify under different aspects, and therefore can lead to different results. We developed a mathematically unique representation of protein structure topologies at a higher abstraction level providing new aspects of classification and enabling for a fast search through the data. Protein Topology Graph Library (PTGL; http://ptgl.zib.de) aims at providing a database on protein secondary structure topologies, including search facilities, the visualization as intuitive topology diagrams as well as in the 3D structure, and additional information. Secondary structure-based protein topologies are represented uniquely as undirected labeled graphs in four different ways allowing for exploration under different aspects. The linear notations, and the 2D and 3D diagrams of each notation facilitate a deeper understanding of protein topologies. Several search functions for topologies and sub-topologies, BLAST search possibility, and links to SCOP, CATH and PDBsum support individual and large-scale investigation of protein structures. Currently, PTGL comprises topologies of 54,859 protein structures. Main structural patterns for common structural motifs like TIM-barrel or Jelly Roll are pre-implemented, and can easily be searched. [less ▲]

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See detailSequence-structure relationships in RNA loops: establishing the basis for loop homology modeling.
Schudoma, Christian; May, Patrick UL; Nikiforova, Viktoria et al

in Nucleic Acids Research (2010), 38(3), 970-80

The specific function of RNA molecules frequently resides in their seemingly unstructured loop regions. We performed a systematic analysis of RNA loops extracted from experimentally determined three ... [more ▼]

The specific function of RNA molecules frequently resides in their seemingly unstructured loop regions. We performed a systematic analysis of RNA loops extracted from experimentally determined three-dimensional structures of RNA molecules. A comprehensive loop-structure data set was created and organized into distinct clusters based on structural and sequence similarity. We detected clear evidence of the hallmark of homology present in the sequence-structure relationships in loops. Loops differing by <25% in sequence identity fold into very similar structures. Thus, our results support the application of homology modeling for RNA loop model building. We established a threshold that may guide the sequence divergence-based selection of template structures for RNA loop homology modeling. Of all possible sequences that are, under the assumption of isosteric relationships, theoretically compatible with actual sequences observed in RNA structures, only a small fraction is contained in the Rfam database of RNA sequences and classes implying that the actual RNA loop space may consist of a limited number of unique loop structures and conserved sequences. The loop-structure data sets are made available via an online database, RLooM. RLooM also offers functionalities for the modeling of RNA loop structures in support of RNA engineering and design efforts. [less ▲]

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See detailAlgebraic connectivity may explain the evolution of gene regulatory networks.
Nikoloski, Zoran; May, Patrick UL; Selbig, Joachim

in Journal of Theoretical Biology (2010), 267(1), 7-14

Gene expression is a result of the interplay between the structure, type, kinetics, and specificity of gene regulatory interactions, whose diversity gives rise to the variety of life forms. As the dynamic ... [more ▼]

Gene expression is a result of the interplay between the structure, type, kinetics, and specificity of gene regulatory interactions, whose diversity gives rise to the variety of life forms. As the dynamic behavior of gene regulatory networks depends on their structure, here we attempt to determine structural reasons which, despite the similarities in global network properties, may explain the large differences in organismal complexity. We demonstrate that the algebraic connectivity, the smallest non-trivial eigenvalue of the Laplacian, of the directed gene regulatory networks decreases with the increase of organismal complexity, and may therefore explain the difference between the variety of analyzed regulatory networks. In addition, our results point out that, for the species considered in this study, evolution favours decreasing concentration of strategically positioned feed forward loops, so that the network as a whole can increase the specificity towards changing environments. Moreover, contrary to the existing results, we show that the average degree, the length of the longest cascade, and the average cascade length of gene regulatory networks cannot recover the evolutionary relationships between organisms. Whereas the dynamical properties of special subnetworks are relatively well understood, there is still limited knowledge about the evolutionary reasons for the already identified design principles pertaining to these special subnetworks, underlying the global quantitative features of gene regulatory networks of different organisms. The behavior of the algebraic connectivity, which we show valid on gene regulatory networks extracted from curated databases, can serve as an additional evolutionary principle of organism-specific regulatory networks. [less ▲]

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See detailModeling RNA loops using sequence homology and geometric constraints.
Schudoma, Christian; May, Patrick UL; Walther, Dirk

in Bioinformatics (2010), 26(13), 1671-2

SUMMARY: RNA loop regions are essential structural elements of RNA molecules influencing both their structural and functional properties. We developed RLooM, a web application for homology-based modeling ... [more ▼]

SUMMARY: RNA loop regions are essential structural elements of RNA molecules influencing both their structural and functional properties. We developed RLooM, a web application for homology-based modeling of RNA loops utilizing template structures extracted from the PDB. RLooM allows the insertion and replacement of loop structures of a desired sequence into an existing RNA structure. Furthermore, a comprehensive database of loops in RNA structures can be accessed through the web interface. AVAILABILITY AND IMPLEMENTATION: The application was implemented in Python, MySQL and Apache. A web interface to the database and loop modeling application is freely available at http://rloom.mpimp-golm.mpg.de CONTACT: schudoma@mpimp-golm.mpg.de; may@mpimp-golm.mpg.de; walther@mpimp-golm.mpg.de [less ▲]

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See detailTargeted proteomics for Chlamydomonas reinhardtii combined with rapid subcellular protein fractionation, metabolomics and metabolic flux analyses.
Wienkoop, Stefanie; Weiss, Julia; May, Patrick UL et al

in Molecular Biosystems (2010), 6(6), 1018-31

In the era of fast genome sequencing a critical goal is to develop genome-wide quantitative molecular approaches. Here, we present a metaproteogenomic strategy to integrate proteomics and metabolomics ... [more ▼]

In the era of fast genome sequencing a critical goal is to develop genome-wide quantitative molecular approaches. Here, we present a metaproteogenomic strategy to integrate proteomics and metabolomics data for systems level analysis in the recently sequenced unicellular green algae Chlamydomonas reinhardtii. To achieve a representative proteome coverage we analysed different growth conditions with protein prefractionation and shotgun proteomics. For protein identification, different genome annotations as well as new gene model predictions with stringent peptide filter criteria were used. An overlapping proteome coverage of 25%, consistent for all databases, was determined. The data are stored in a public mass spectral reference database ProMEX (http://www.promexdb.org/home.shtml). A set of proteotypic peptides comprising Calvin cycle, photosynthetic apparatus, starch synthesis, glycolysis, TCA cycle, carbon concentrating mechanisms (CCM) and other pathways was selected from this database for targeted proteomics (Mass Western). Rapid subcellular fractionation in combination with targeted proteomics allowed for measuring subcellular protein concentrations in attomole per 1000 cells. From the same samples metabolite concentrations and metabolic fluxes by stable isotope incorporation were analyzed. Differences were found in the growth-dependent crosstalk of chloroplastidic and mitochondrial metabolism. A Mass Western survey of all detectable carbonic anhydrases partially involved in carbon-concentrating mechanism (CCM) revealed highest internal cell concentrations for a specific low-CO2-inducible mitochondrial CAH isoform. This indicates its role as one of the strongest CO2-responsive proteins in the crosstalk of air-adapted mixotrophic chloroplast and mitochondrial metabolism in Chlamydomonas reinhardtii. [less ▲]

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See detailIdentification and classification of ncRNA molecules using graph properties.
Childs, Liam; Nikoloski, Zoran; May, Patrick UL et al

in Nucleic Acids Research (2009), 37(9), 66

The study of non-coding RNA genes has received increased attention in recent years fuelled by accumulating evidence that larger portions of genomes than previously acknowledged are transcribed into RNA ... [more ▼]

The study of non-coding RNA genes has received increased attention in recent years fuelled by accumulating evidence that larger portions of genomes than previously acknowledged are transcribed into RNA molecules of mostly unknown function, as well as the discovery of novel non-coding RNA types and functional RNA elements. Here, we demonstrate that specific properties of graphs that represent the predicted RNA secondary structure reflect functional information. We introduce a computational algorithm and an associated web-based tool (GraPPLE) for classifying non-coding RNA molecules as functional and, furthermore, into Rfam families based on their graph properties. Unlike sequence-similarity-based methods and covariance models, GraPPLE is demonstrated to be more robust with regard to increasing sequence divergence, and when combined with existing methods, leads to a significant improvement of prediction accuracy. Furthermore, graph properties identified as most informative are shown to provide an understanding as to what particular structural features render RNA molecules functional. Thus, GraPPLE may offer a valuable computational filtering tool to identify potentially interesting RNA molecules among large candidate datasets. [less ▲]

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See detailChlamyCyc: an integrative systems biology database and web-portal for Chlamydomonas reinhardtii.
May, Patrick UL; Christian, Jan-Ole; Kempa, Stefan et al

in BMC Genomics (2009), 10

BACKGROUND: The unicellular green alga Chlamydomonas reinhardtii is an important eukaryotic model organism for the study of photosynthesis and plant growth. In the era of modern high-throughput ... [more ▼]

BACKGROUND: The unicellular green alga Chlamydomonas reinhardtii is an important eukaryotic model organism for the study of photosynthesis and plant growth. In the era of modern high-throughput technologies there is an imperative need to integrate large-scale data sets from high-throughput experimental techniques using computational methods and database resources to provide comprehensive information about the molecular and cellular organization of a single organism. RESULTS: In the framework of the German Systems Biology initiative GoFORSYS, a pathway database and web-portal for Chlamydomonas (ChlamyCyc) was established, which currently features about 250 metabolic pathways with associated genes, enzymes, and compound information. ChlamyCyc was assembled using an integrative approach combining the recently published genome sequence, bioinformatics methods, and experimental data from metabolomics and proteomics experiments. We analyzed and integrated a combination of primary and secondary database resources, such as existing genome annotations from JGI, EST collections, orthology information, and MapMan classification. CONCLUSION: ChlamyCyc provides a curated and integrated systems biology repository that will enable and assist in systematic studies of fundamental cellular processes in Chlamydomonas. The ChlamyCyc database and web-portal is freely available under http://chlamycyc.mpimp-golm.mpg.de. [less ▲]

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See detailJAIL: a structure-based interface library for macromolecules.
Gunther, Stefan; von Eichborn, Joachim; May, Patrick UL et al

in Nucleic Acids Research (2009), 37(Database issue), 338-41

The increasing number of solved macromolecules provides a solid number of 3D interfaces, if all types of molecular contacts are being considered. JAIL annotates three different kinds of macromolecular ... [more ▼]

The increasing number of solved macromolecules provides a solid number of 3D interfaces, if all types of molecular contacts are being considered. JAIL annotates three different kinds of macromolecular interfaces, those between interacting protein domains, interfaces of different protein chains and interfaces between proteins and nucleic acids. This results in a total number of about 184,000 database entries. All the interfaces can easily be identified by a detailed search form or by a hierarchical tree that describes the protein domain architectures classified by the SCOP database. Visual inspection of the interfaces is possible via an interactive protein viewer. Furthermore, large scale analyses are supported by an implemented sequential and by a structural clustering. Similar interfaces as well as non-redundant interfaces can be easily picked out. Additionally, the sequential conservation of binding sites was also included in the database and is retrievable via Jmol. A comprehensive download section allows the composition of representative data sets with user defined parameters. The huge data set in combination with various search options allow a comprehensive view on all interfaces between macromolecules included in the Protein Data Bank (PDB). The download of the data sets supports numerous further investigations in macromolecular recognition. JAIL is publicly available at http://bioinformatics.charite.de/jail. [less ▲]

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See detailIdentification of nutrient-responsive Arabidopsis and rapeseed microRNAs by comprehensive real-time polymerase chain reaction profiling and small RNA sequencing.
Pant, Bikram Datt; Musialak-Lange, Magdalena; Nuc, Przemyslaw et al

in Plant Physiology (2009), 150(3), 1541-55

Comprehensive expression profiles of Arabidopsis (Arabidopsis thaliana) MIRNA genes and mature microRNAs (miRs) are currently not available. We established a quantitative real-time polymerase chain ... [more ▼]

Comprehensive expression profiles of Arabidopsis (Arabidopsis thaliana) MIRNA genes and mature microRNAs (miRs) are currently not available. We established a quantitative real-time polymerase chain reaction platform that allows rapid and sensitive quantification of 177 Arabidopsis primary miR transcripts (pri-miRs). The platform was used to detect phosphorus (P) or nitrogen (N) status-responsive pri-miR species. Several pri-miR169 species as well as pri-miR398a were found to be repressed during N limitation, whereas during P limitation, pri-miR778, pri-miR827, and pri-miR399 species were induced and pri-miR398a was repressed. The corresponding responses of the biologically active, mature miRs were confirmed using specific stem-loop reverse transcription primer quantitative polymerase chain reaction assays and small RNA sequencing. Interestingly, the latter approach also revealed high abundance of some miR star strands. Bioinformatic analysis of small RNA sequences with a modified miRDeep algorithm led to the identification of the novel P limitation-induced miR2111, which is encoded by two loci in the Arabidopsis genome. Furthermore, miR2111, miR169, a miR827-like sequence, and the abundances of several miR star strands were found to be strongly dependent on P or N status in rapeseed (Brassica napus) phloem sap, flagging them as candidate systemic signals. Taken together, these results reveal the existence of complex small RNA-based regulatory networks mediating plant adaptation to mineral nutrient availability. [less ▲]

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See detailChlamyCyc--a comprehensive database and web-portal centered on Chlamydomonas reinhardtii
Christian, Jan-Ole; May, Patrick UL; Kempa, Stefan et al

Poster (2009)

Background – The unicellular green alga Chlamydomonas reinhardtii is an important eukaryotic model organism for the study of photosynthesis and growth, as well as flagella development and other cellular ... [more ▼]

Background – The unicellular green alga Chlamydomonas reinhardtii is an important eukaryotic model organism for the study of photosynthesis and growth, as well as flagella development and other cellular processes. In the era of high-throughput technologies there is an imperative need to integrate large-scale data sets from high-throughput experimental techniques using computational methods and database resources to provide comprehensive information about the whole cellular system of a single organism. Results – In the framework of the German Systems Biology initiative GoFORSYS a pathway/genome database and web-portal for Chlamydomonas reinhardtii (ChlamyCyc) was established, which currently features about 270 metabolic pathways with related genes, enzymes, and compound information. ChlamyCyc was assembled using an integrative approach combining the recently published genome sequence, bioinformatics methods, and experimental data from metabolomics and proteomics experiments. We analyzed and integrated a combination of primary and secondary database resources, such as existing genome annotations from JGI, EST collections, orthology information, and MapMan classification. Conclusion – Chlamycyc provides a curated and integrated systems biology repository that will enable and assist in systematic studies of fundamental cellular processes in Chlamydomonas reinhardtii. The ChlamyCyc database and web-portal is freely available under http://chlamycyc.mpimp-golm.mpg.de. [less ▲]

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See detailAn integrative approach towards completing genome-scale metabolic networks.
Christian, Nils UL; May, Patrick UL; Kempa, Stefan et al

in Molecular Biosystems (2009), 5(12), 1889-903

Genome-scale metabolic networks which have been automatically derived through sequence comparison techniques are necessarily incomplete. We propose a strategy that incorporates genomic sequence data and ... [more ▼]

Genome-scale metabolic networks which have been automatically derived through sequence comparison techniques are necessarily incomplete. We propose a strategy that incorporates genomic sequence data and metabolite profiles into modeling approaches to arrive at improved gene annotations and more complete genome-scale metabolic networks. The core of our strategy is an algorithm that computes minimal sets of reactions by which a draft network has to be extended in order to be consistent with experimental observations. A particular strength of our approach is that alternative possibilities are suggested and thus experimentally testable hypotheses are produced. We carefully evaluate our strategy on the well-studied metabolic network of Escherichia coli, demonstrating how the predictions can be improved by incorporating sequence data. Subsequently, we apply our method to the recently sequenced green alga Chlamydomonas reinhardtii. We suggest specific genes in the genome of Chlamydomonas which are the strongest candidates for coding the responsible enzymes. [less ▲]

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See detailMetabolomics- and proteomics-assisted genome annotation and analysis of the draft metabolic network of Chlamydomonas reinhardtii.
May, Patrick UL; Wienkoop, Stefanie; Kempa, Stefan et al

in Genetics (2008), 179(1), 157-66

We present an integrated analysis of the molecular repertoire of Chlamydomonas reinhardtii under reference conditions. Bioinformatics annotation methods combined with GCxGC/MS-based metabolomics and LC/MS ... [more ▼]

We present an integrated analysis of the molecular repertoire of Chlamydomonas reinhardtii under reference conditions. Bioinformatics annotation methods combined with GCxGC/MS-based metabolomics and LC/MS-based shotgun proteomics profiling technologies have been applied to characterize abundant proteins and metabolites, resulting in the detection of 1069 proteins and 159 metabolites. Of the measured proteins, 204 currently do not have EST sequence support; thus a significant portion of the proteomics-detected proteins provide evidence for the validity of in silico gene models. Furthermore, the generated peptide data lend support to the validity of a number of proteins currently in the proposed model stage. By integrating genomic annotation information with experimentally identified metabolites and proteins, we constructed a draft metabolic network for Chlamydomonas. Computational metabolic modeling allowed an identification of missing enzymatic links. Some experimentally detected metabolites are not producible by the currently known and annotated enzyme set, thus suggesting entry points for further targeted gene discovery or biochemical pathway research. All data sets are made available as supplementary material as well as web-accessible databases and within the functional context via the Chlamydomonas-adapted MapMan annotation platform. Information of identified peptides is also available directly via the JGI-Chlamydomonas genomic resource database (http://genome.jgi-psf.org/Chlre3/Chlre3.home.html). [less ▲]

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See detailMetabolic networks are NP-hard to reconstruct.
Nikoloski, Zoran; Grimbs, Sergio; May, Patrick UL et al

in Journal of Theoretical Biology (2008), 254(4), 807-16

High-throughput data from various omics and sequencing techniques have rendered the automated metabolic network reconstruction a highly relevant problem. Our approach reflects the inherent probabilistic ... [more ▼]

High-throughput data from various omics and sequencing techniques have rendered the automated metabolic network reconstruction a highly relevant problem. Our approach reflects the inherent probabilistic nature of the steps involved in metabolic network reconstruction. Here, the goal is to arrive at networks which combine probabilistic information with the possibility to obtain a small number of disconnected network constituents by reduction of a given preliminary probabilistic metabolic network. We define automated metabolic network reconstruction as an optimization problem on four-partite graph (nodes representing genes, enzymes, reactions, and metabolites) which integrates: (1) probabilistic information obtained from the existing process for metabolic reconstruction from a given genome, (2) connectedness of the raw metabolic network, and (3) clustering of components in the reconstructed metabolic network. The practical implications of our theoretical analysis refer to the quality of reconstructed metabolic networks and shed light on the problem of finding more efficient and effective methods for automated reconstruction. Our main contributions include: a completeness result for the defined problem, polynomial-time approximation algorithm, and an optimal polynomial-time algorithm for trees. Moreover, we exemplify our approach by the reconstruction of the sucrose biosynthesis pathway in Chlamydomonas reinhardtii. [less ▲]

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See detailAccelerated microRNA-Precursor Detection Using the Smith-Waterman Algorithm on FPGAs
May, Patrick UL; Klau, Gunnar W.; Bauer, Markus et al

in Dubitzky, Werner; Schuster, Assaf; Sloot, Peterm A. (Eds.) et al Distributed, High-Performance and Grid Computing in Computational Biology (2007)

During the last few years more and more functionalities of RNA have been discovered that were previously thought of being carried out by proteins alone. One of the most striking discoveries was the ... [more ▼]

During the last few years more and more functionalities of RNA have been discovered that were previously thought of being carried out by proteins alone. One of the most striking discoveries was the detection of microRNAs, a class of noncoding RNAs that play an important role in post-transcriptional gene regulation. Large-scale analyses are needed for the still increasingly growing amount of sequence data derived from new experimental technologies. In this paper we present a framework for the detection of the distinctive precursor structure of microRNAS that is based on the well-known Smith-Waterman algorithm. By conducting the computation of the local alignment on a FPGA, we are able to gain a substantial speedup compared to a pure software implementation bringing together supercomputer performance and bioinformatics research. We conducted experiments on real genomic data and we found several new putative hits for microRNA precursor structures. [less ▲]

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See detailDocking without docking: ISEARCH--prediction of interactions using known interfaces.
Gunther, Stefan; May, Patrick UL; Hoppe, Andreas et al

in Proteins (2007), 69(4), 839-44

The increasing number of solved protein structures provides a solid number of interfaces, if protein-protein interactions, domain-domain contacts, and contacts between biological units are taken into ... [more ▼]

The increasing number of solved protein structures provides a solid number of interfaces, if protein-protein interactions, domain-domain contacts, and contacts between biological units are taken into account. An interface library gives us the opportunity to identify surface regions on a target molecule that are similar by local structure and residue composition. If both unbound components of a possible protein complex exhibit structural similarities to a known interface, the unbound structures can be superposed onto the known interfaces. The approach is accompanied by two mathematical problems. Protein surfaces have to be quickly screened by thousands of patches, and similarity has to be evaluated by a suitable scoring scheme. The used algorithm (NeedleHaystack) identifies similar patches within minutes. Structurally related sites are recognized even if only parts of the template patches are structurally related to the interface region. A successful prediction of the protein complex depends on a suitable template of the library. However, the performed tests indicate that interaction sites are identified even if the similarity is very low. The approach complements existing ab initio methods and provides valuable results on standard benchmark sets. [less ▲]

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See detailZIB Structure Prediction Pipeline: Composing a Complex Biological Workflow through Web Services
May, Patrick UL; Ehrlich, Hans-Christian; Steinke, Thomas

in Nagel, Wolfgang E.; Walter, Wolfgang V.; Lehner, Wolfgang (Eds.) Euro-Par 2006 Parallel Processing (2006)

In life sciences, scientists are confronted with an exponential growth of biological data, especially in the genomics and proteomics area. The efficient management and use of these data, and its ... [more ▼]

In life sciences, scientists are confronted with an exponential growth of biological data, especially in the genomics and proteomics area. The efficient management and use of these data, and its transformation into knowledge are basic requirements for biological research. Therefore, integration of diverse applications and data from geographically distributed computing resources will become a major issue. We will present the status of our efforts for the realization of an automated protein prediction pipeline as an example for a complex biological workflow scenario in a Grid environment based on Web services. This case study demonstrates the ability of an easy orchestration of complex biological workflows based on Web services as building blocks and Triana as workflow engine. [less ▲]

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See detailConnectivity independent protein-structure alignment: a hierarchical approach.
Kolbeck, Bjoern; May, Patrick UL; Schmidt-Goenner, Tobias et al

in BMC Bioinformatics (2006), 7

BACKGROUND: Protein-structure alignment is a fundamental tool to study protein function, evolution and model building. In the last decade several methods for structure alignment were introduced, but most ... [more ▼]

BACKGROUND: Protein-structure alignment is a fundamental tool to study protein function, evolution and model building. In the last decade several methods for structure alignment were introduced, but most of them ignore that structurally similar proteins can share the same spatial arrangement of secondary structure elements (SSE) but differ in the underlying polypeptide chain connectivity (non-sequential SSE connectivity). RESULTS: We perform protein-structure alignment using a two-level hierarchical approach implemented in the program GANGSTA. On the first level, pair contacts and relative orientations between SSEs (i.e. alpha-helices and beta-strands) are maximized with a genetic algorithm (GA). On the second level residue pair contacts from the best SSE alignments are optimized. We have tested the method on visually optimized structure alignments of protein pairs (pairwise mode) and for database scans. For a given protein structure, our method is able to detect significant structural similarity of functionally important folds with non-sequential SSE connectivity. The performance for structure alignments with strictly sequential SSE connectivity is comparable to that of other structure alignment methods. CONCLUSION: As demonstrated for several applications, GANGSTA finds meaningful protein-structure alignments independent of the SSE connectivity. GANGSTA is able to detect structural similarity of protein folds that are assigned to different superfamilies but nevertheless possess similar structures and perform related functions, even if these proteins differ in SSE connectivity. [less ▲]

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See detailA computational approach to microRNA detection
May, Patrick UL; Bauer, Markus; Köberle, Christian et al

Report (2006)

During the last few years more and more functionalities of RNA have been discovered that were previously thought of being carried out by proteins alone. One of the most striking discoveries was the de ... [more ▼]

During the last few years more and more functionalities of RNA have been discovered that were previously thought of being carried out by proteins alone. One of the most striking discoveries was the de tection of microRNAs, a class of noncoding RNAs that play an important role in post-transcriptional gene regulation. Large-scale analyses are needed for the still increasingly growing amount of sequen ce data derived from new experimental technologies. In this paper we present a framework for the detection of the distinctive precursor structure of microRNAS that is based on the well-known Smith-Wat erman algorithm and various filtering steps. We conducted experiments on real genomic data and we found several new putative hits for microRNA precursor structures. [less ▲]

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