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Neurodegeneration and Cancer: Where the Disorder Prevails

Petr Klus, Davide Cirillo, Teresa Botta Orfila, Gian Gaetano Tartaglia
2015 Scientific Reports  
It has been reported that genes up-regulated in cancer are often down-regulated in neurodegenerative disorders and vice versa. The fact that apparently unrelated diseases share functional pathways suggests a link between their etiopathogenesis and the properties of molecules involved. Are there specific features that explain the exclusive association of proteins with either cancer or neurodegeneration? We performed a large-scale analysis of physico-chemical properties to understand what
more » ... ristics differentiate classes of diseases. We found that structural disorder significantly distinguishes proteins up-regulated in neurodegenerative diseases from those linked to cancer. We also observed high correlation between structural disorder and age of onset in Frontotemporal Dementia, Parkinson's and Alzheimer's diseases, which strongly supports the role of protein unfolding in neurodegenerative processes. It has been reported that tumor suppressor p53 has physico-chemical features that are typical of prionoid proteins associated with neurodegenerative diseases 1 . This finding is particularly interesting because it suggests that common molecular properties can be linked to relatively distant diseases. As a matter of fact, a recent study by Ibáñez et al. 2 shows that transcripts up-regulated in cancer are down-regulated in central nervous system (CNS) diseases and vice versa. In line with this finding, a risk reduction for some cancer types has been observed in patients affected by Parkinson's 3 and Alzheimer's diseases 4 . Are there common physico-chemical determinants behind comorbidities? We re-analysed the data published by Ibáñez et al. 2 to understand if differential regulation of genes can be associated with specific protein features. While the original study by Ibáñez et al. 2 focused on transcripts that are exclusively up-regulated in cancer and down-regulated in CNS diseases and vice versa 2 , our analysis deals with genes that are exclusively associated with either CNS diseases or cancer (Fig. 1 ). In agreement with recent experimental findings 5 and theoretical analyses 6-9 , we investigated the physico-chemical properties of gene products assuming a proportionality between transcript and protein abundances.
doi:10.1038/srep15390 pmid:26493371 pmcid:PMC4615981 fatcat:fogi353a4ngatdnxv2ord6vewq

catRAPIDsignature: identification of ribonucleoproteins and RNA-binding regions

Carmen Maria Livi, Petr Klus, Riccardo Delli Ponti, Gian Gaetano Tartaglia
2015 Bioinformatics  
., 2011) to predict protein-RNA interactions and the cleverSuite algorithm (Klus et al., 2014) to classify protein groups using physico-chemical features.  ...  ALGORITHM AND PERFORMANCES To build catRAPID signature we exploited a number of physico-chemical properties reported in our previous publication (Klus et al., 2014) : • We used each physico-chemical property  ... 
doi:10.1093/bioinformatics/btv629 pmid:26520853 pmcid:PMC4795616 fatcat:n2aykgtr3nbe3jqmg5bxpbe47q

Non-random distribution of homo-repeats: links with biological functions and human diseases

Michail Yu. Lobanov, Petr Klus, Igor V. Sokolovsky, Gian Gaetano Tartaglia, Oxana V. Galzitskaya
2016 Scientific Reports  
The biological function of multiple repetitions of single amino acids, or homo-repeats, is largely unknown, but their occurrence in proteins has been associated with more than 20 hereditary diseases. Analysing 122 bacterial and eukaryotic genomes, we observed that the number of proteins containing homo-repeats is significantly larger than expected from theoretical estimates. Analysis of statistical significance indicates that the minimal size of homo-repeats varies with amino acid type and
more » ... ome. In an attempt to characterize proteins harbouring long homo-repeats, we found that those containing polar or small amino acids S, P, H, E, D, K, Q and N are enriched in structural disorder as well as proteinand RNA-interactions. We observed that E, S, Q, G, L, P, D, A and H homo-repeats are strongly linked with occurrence in human diseases. Moreover, S, E, P, A, Q, D and T homo-repeats are significantly enriched in neuronal proteins associated with autism and other disorders. We release a webserver for further exploration of homo-repeats occurrence in human pathology at http://bioinfo.protres.ru/ hradis/. Eukaryotic and bacterial genomes harbour proteins containing multiple repetitions of specific amino acids called homo-repeats. The functional role of homo-repeats is still unclear 1 , although a tight link with disease exists 2 . Homo-repeat sizes vary from proteome to proteome 3,4 and are associated with low complexity regions in eukaryotes 5 . Indeed, comparing H. sapiens and E. coli proteins, we previously reported a significant enrichment of homo-repeats in H. sapiens 6 , which can be linked to the presence of structurally disordered regions 7 . Some homo-repeats, such as for instance LLLLLL, occur 11 times more frequently in H. sapiens than D. melanogaster and C. elegans, while TTTTTT are 4 times more abundant in D. melanogaster and C. elegans than H. sapiens 8 . Similarly, the poly-N motif occurs more than 17000 times in 122 proteomes 3 : The NNNNN pattern is connected with fungi symbiosis and occurs 21 times in the human proteome 3 . Also HHHHHH repeats are particularly frequent, especially at the N-or C-terminus of polypeptide chains, but their abundance in crystal and NMR structures is often due to biochemical procedures (histidine-tags are useful for purification at a nickel-containing column) 9 . Yet, poly-H are highly frequent in the human proteome and linked to a number of functional roles 6 . For instance, protein kinase DYRK1A (poly-H length of 13) and FAM76B (poly-H length of 10) uses histidine expansions to mediate nuclear speckle trafficking 10-12 . What functions of poly-repeats are known? For instance, poly-L expansions, especially when located at the N-terminal end of proteins 13 , act as signal peptides and are abundant in membrane proteins 14 . By contrast, poly-Q and poly-A occur more often in transcription factors and poly-K are enriched in a number of metabolic pathways 3 . Similarly, poly-M are connected with voltage-gated calcium channel activity 3 , while poly-P are associated with central nervous system, morphogenesis and through actin cytoskeleton organization, cell morphogenesis, tropomyosin binding and stereocilium 3 . The poly-A tract in the HOXD13 human protein (15 residues in length) is essential for limb development 11 . Not all homo-repeats are associated with specific roles and investigation of their biological functions is complicated by the widespread occurrence in low-complexity regions of higher eukaryotes 15 . Here, we studied
doi:10.1038/srep26941 pmid:27256590 pmcid:PMC4891720 fatcat:xetjwbcsj5axnfwp7ooeow7zre

BarraCUDA - a fast short read sequence aligner using graphics processing units

Petr Klus, Simon Lam, Dag Lyberg, Ming Cheung, Graham Pullan, Ian McFarlane, Giles SH Yeo, Brian YH Lam
2012 BMC Research Notes  
With the maturation of next-generation DNA sequencing (NGS) technologies, the throughput of DNA sequencing reads has soared to over 600 gigabases from a single instrument run. General purpose computing on graphics processing units (GPGPU), extracts the computing power from hundreds of parallel stream processors within graphics processing cores and provides a cost-effective and energy efficient alternative to traditional high-performance computing (HPC) clusters. In this article, we describe the
more » ... implementation of BarraCUDA, a GPGPU sequence alignment software that is based on BWA, to accelerate the alignment of sequencing reads generated by these instruments to a reference DNA sequence. Findings: Using the NVIDIA Compute Unified Device Architecture (CUDA) software development environment, we ported the most computational-intensive alignment component of BWA to GPU to take advantage of the massive parallelism. As a result, BarraCUDA offers a magnitude of performance boost in alignment throughput when compared to a CPU core while delivering the same level of alignment fidelity. The software is also capable of supporting multiple CUDA devices in parallel to further accelerate the alignment throughput. Conclusions: BarraCUDA is designed to take advantage of the parallelism of GPU to accelerate the alignment of millions of sequencing reads generated by NGS instruments. By doing this, we could, at least in part streamline the current bioinformatics pipeline such that the wider scientific community could benefit from the sequencing technology. BarraCUDA is currently available from http://seqbarracuda.sf.net
doi:10.1186/1756-0500-5-27 pmid:22244497 pmcid:PMC3278344 fatcat:bj2of2zssneppongs6aylsaonq

The Effect of Trace Oxygen Addition on the Interface Behavior of Low-Alloy Steel

Vlastimil Novák, Lenka Řeháčková, Petra Váňová, Michal Sniegoň, Dalibor Matýsek, Kateřina Konečná, Bedřich Smetana, Silvie Rosypalová, Markéta Tkadlečková, Ľubomíra Drozdová, Petr Klus
2022 Materials  
This work aims to assess the effect of an oxygen content graded in minimal quantities, on the order of hundreds of ppms, on the determination of surface tension of low-alloy FeCOCr and FeCONi steels in contact with a corundum substrate. Oxygen, as a surface-active element, was segregated at the surface where it interacted with the major components of the alloys, leading to a reduction in surface tension. The sessile drop method was used for wetting tests in the temperature range from steel
more » ... dus temperatures to 1600 °C under nonoxidizing conditions. The effect of oxygen on surface tension and wetting angles was verified by statistical analysis using the Kruskal–Wallis test, which supported the results stating that the values of these quantities decreased with increasing oxygen content. Furthermore, liquidus temperatures, which are of practical importance, were determined by the optical and DTA methods and then compared with theoretically calculated temperature values. It turned out that the increased chromium content causes difficulties in determining surface tension up to 1550 °C due to the formation of a thin Cr2O3 layer. In addition, SEM and XRD analyses accompanied by calculations in the FactSage oxide database were performed to better understand the wetting mechanism.
doi:10.3390/ma15041592 pmid:35208132 pmcid:PMC8875985 fatcat:q4ktfimnhzdg7lfbwb5nhqaxo4

Protein aggregation, structural disorder and RNA-binding ability: a new approach for physico-chemical and gene ontology classification of multiple datasets

Petr Klus, Riccardo Delli Ponti, Carmen Maria Livi, Gian Gaetano Tartaglia
2015 BMC Genomics  
Comparison between multiple protein datasets requires the choice of an appropriate reference system and a number of variables to describe their differences. Here we introduce an innovative approach to discriminate multiple protein datasets (multiCM) and to measure enrichments in gene ontology terms (cleverGO) using semantic similarities. Results: We illustrate the powerfulness of our approach by investigating the links between RNA-binding ability and other protein features, such as structural
more » ... sorder and aggregation, in S. cerevisiae, C. elegans, M. musculus and H. sapiens. Our results are in striking agreement with available experimental evidence and unravel features that are key to understand the mechanisms regulating cellular homeostasis. Conclusions: In an intuitive way, multiCM and cleverGO provide accurate classifications of physico-chemical features and annotations of biological processes, molecular functions and cellular components, which is extremely useful for the discovery and characterization of new trends in protein datasets. The multiCM and cleverGO can be freely accessed on the Web at
doi:10.1186/s12864-015-2280-z pmid:26673865 pmcid:PMC4681139 fatcat:ddkg6z6zi5gdvpiore5ezqmrhy

The cleverSuite approach for protein characterization: predictions of structural properties, solubility, chaperone requirements and RNA-binding abilities

Petr Klus, Benedetta Bolognesi, Federico Agostini, Domenica Marchese, Andreas Zanzoni, Gian Gaetano Tartaglia
2014 Computer applications in the biosciences : CABIOS  
Motivation: The recent shift towards high-throughput screening is posing new challenges for the interpretation of experimental results. Here we propose the cleverSuite approach for large-scale characterization of protein groups. Description: The central part of the cleverSuite is the cleverMachine, an algorithm that performs statistics on protein sequences by comparing their physico-chemical propensities. The second element is called cleverClassifier and builds on top of the models generated by
more » ... the cleverMachine to allow classification of new datasets. Results: We applied the cleverSuite to predict secondary structure properties, solubility, chaperone requirements and RNA-binding abilities. Using cross-validation and independent datasets, the cleverSuite reproduces experimental findings with great accuracy and provides models that can be used for future investigations. The intuitive interface for dataset exploration, analysis and prediction is available at http://s.tartaglialab.com/clever_suite. Contact: gian.tartaglia@crg.es Supplementary information: Supplementary data are available at Bioinformatics online Our approach, the cleverSuite, provides a series of easy-to-use, configuration-free tools with interactive graphical interface. The central part of the suite is the cleverMachine (CM), an algorithm to characterize protein datasets. CM does not require external fitting parameters and returns multiple physico-chemical properties
doi:10.1093/bioinformatics/btu074 pmid:24493033 pmcid:PMC4029037 fatcat:2mugtv52wrfs3jyrycjv4p3dle

Experimental verification of hematite ingot mould heat capacity and its direct utilisation in simulation of casting process

Bedřich Smetana, Monika Žaludová, Markéta Tkadlečková, Jana Dobrovská, Simona Zlá, Karel Gryc, Petr Klus, Karel Michalek, Pavel Machovčák, Lenka Řeháčková
2013 Journal of thermal analysis and calorimetry (Print)  
00420 597 321 594 00420 597 323 396 bedrich.smetana@vsb.cz XXXXXXX URL Article note Heat capacity of alloys (metals) is one of the crucial thermo-physical parameters used for process behaviour prediction in many applications. Heat capacity is an input variable for many thermo-dynamical (e.g. Thermocalc, Pandat, MTData,...) and kinetic programs (e.g. IDS-Solidification analysis package,...). The dependences of heat capacity on common variables (temperature, pressure) are also commonly used as
more » ... input data in software packages (e.g. ProCast, Magmasoft, ANSYS Fluent...) that are applicable in the field of applied research for simulations of technological processes. It follows from the above that the heat capacities of materials, in our case alloys, play a very important role in the field of basic and applied research. Generally speaking, experimental data can be found in the literature, but corresponding (needed) data for the given alloy can very seldomly be found or can differ from the tabulated ones. The knowledge of proper values of heat capacities of alloys at the corresponding temperature can be substantially used for addition to and thus towards the precision of the existing database and simulation software. The paper presents the values of C p measured for the hematite ingot mould and comparison of the measured data with the C p obtained using the software CompuTherm with respect to simulation of technological casting process.
doi:10.1007/s10973-013-2964-z fatcat:q62pnpzivngi3ez5eixb5pzn3i

NUMERICAL MODELLING OF BLAST FURNACE GAS FLOW IN WATER SEPARATOR

Markéta TKADLEČKOVÁ, Petr KLUS, Petr FARUZEL, Karel MICHALEK, Jiří KRUMPHOLZ
2019 METAL 2019 Conference Proeedings   unpublished
doi:10.37904/metal.2019.798 fatcat:tm65bggx5rhsreyflevvg5pdl4

Experimental study of thermoplastic properties of agglomerate

Vlastimil NOVÁK, Lenka ŘEHÁČKOVÁ, Petr KLUS, Bedřich SMETANA, Silvie ROSYPALOVÁ, Ľubomíra DROZDOVÁ, Jana DOBROVSKÁ
2020 METAL 2020 Conference Proeedings   unpublished
Traditional routes of ironmaking and steelmaking processes demand high-temperature preparatory steps, such as coking and sintering. These processes are of great concern since they represent a considerable environmental burden. As an alternative, carbon-containing iron oxides agglomerates (sinters) can be used. In this work, the assessment of thermoplastic properties of prepared sinters, especially the determination of softening and liquidus temperatures, was performed by two methods: optical
more » ... spindle drop method. For the first-mentioned method, high-temperature observation furnace CLASIC was employed, which enables observation of changes in specimen shape depending on temperature. While in the case of the second method, Furnace Rheometer System FRS 1600 was used. This system allows measuring changes of spindle height as a function of temperature when different normal forces, in specific 3 and 20 N, are applied. Besides, analyzed sinters were of different grain sizes and contained approximately 59 wt.% of iron and 7.2 wt.% of iron(II) oxide. The samples were measured up to liquidus temperature at various heating rates in an inert atmosphere of argon gas. In summary, a good agreement between phase transformation temperatures measured by both methods was achieved, and the influence of experimental conditions on these temperatures was confirmed.
doi:10.37904/metal.2020.3449 fatcat:ixs2xwsks5bslle4dk2pitguci

Verzeichnis der geologischen, paläontologischen, petrographischen und mineralogischen Vorlesungen an den deutschen Hochschulen im S.-S. 1922

1922 Geologische Rundschau  
-petr. Exk., Anl. (Min., Petr.), B~sprechung ausgewiihite r Kapitel aus der Kristallographie, Min. und Petr. 1; KLu~E: Morphologische Ub., m. Exk.  ...  (Geometrische und physikalische Kri- stallographie) 4, Kristallographisehe ~lb. 2, min. oder petr. ~b. 3--6, Anl. (Min., Petr.); SOELLNEE: Lagerstatteu der b~ichterze (mit Auswahl) 2, ~b.  ... 
doi:10.1007/bf01799776 fatcat:4ghfqfemffdpppogqy265brcbe

Checklist of vascular plants from Batu Caves, Selangor, Malaysia

Ruth Kiew
2014 Check List  
-Petr.) Merr. Mohd Nur 8962 FAMILY/ SPECIES ENDEMISM E/TE CALCIPHILE STATUS U/R COLLECTOR, NUMBER Lycophytes Selaginellaceae Selaginella alutacia Spring.  ...  Extraction of data from KLU was done manually from accession books. In the case of dubious identifications, the herbarium specimen was checked and the name corrected.  ... 
doi:10.15560/10.6.1420 fatcat:bbv5ubxe75d7jlod4qmdldrbcu

Page 617 of National Union Catalog Vol. 35, Issue [page]

1958 National Union Catalog  
Petr Zenk!: Socidlni poji- atini v CO. S. R. Woodside, N. Y., Ustiedi svobodnfch ee k¥ch odberd ,195 30, 23 28cm. (1. sv.  ...  Icu ‘OCH MH ‘NNC NIC CLL InU RPB cty Pétss, J Cina par augstim zi zaju séklu razam; Igauni jas PSR Antslas rajona kol ‘Edasi" - u s@klu audz@Sana. Rid, Latvijas Valsts levnieciba, 1956. 48 p.  ... 

Evaluating the computing efficiencies (specificity and sensitivity) of graphics processing unit (GPU)-accelerated DNA sequence alignment tools against central processing unit (CPU) alignment tool
English

Pawar Shrikant, Stanam Aditya, Zhu Ying
2018 Journal of Bioinformatics and Sequence Analysis  
Furthermore, just by using BarraCUDA with two GPUs can outperformed BWA using all 12 cores (2 × Xeon X5670s) at 2.5 Mbp/s (Petr Klus et al., 2012) .  ...  Klus et al., 2012) .  ... 
doi:10.5897/jbsa2018.0109 fatcat:lztw2en25rdxpefmq4s3ma566m

Author Index

2020 2020 12th International Congress on Ultra Modern Telecommunications and Control Systems and Workshops (ICUMT)  
280 Search for Coordinates of WSN Nodes using Multidimensional Scaling Method ICUMT2020 -IH .l 269 Intelligent System Architecture for Smart City and its Applications Based Edge Computing Klus  ...  Recognition Shestakov, Alexander 99 Design of Advanced Slow Denial o f Service Attack Generator119 Applying Machine Learning to LTE Traffic Prediction: Comparison ofBagging, Random Forest, and SVM Dzurenda, Petr  ... 
doi:10.1109/icumt51630.2020.9222462 fatcat:2ywohj2gejcdha52xa4s5qmeg4
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