Domain discovery method for topological profile searches in protein structures

We describe a method for automated domain discovery for topological profile searches in protein structures. The method is used in a system TOPStructure for fast prediction of CATH classification for protein structures (given as PDB files). It is important for profile searches in multi-domain proteins, for which the profile method by itself tends to perform poorly. We also present an O(C(n)k +nk2) time algorithm for this problem, compared to the O(C(n)k +(nk)2) time used by a trivial algorithm (where n is the length of the structure, k is the number of profiles and C(n) is the time needed to check for a presence of a given motif in a structure of length n). This method has been developed and is currently used for TOPS representations of protein structures and prediction of CATH classification, but may be applied to other graph-based representations of protein or RNA structures and/or other prediction problems. A protein structure prediction system incorporating the domain discovery method is available at http://bioinf.mii.lu.lv/tops/

A computer system to perform structure comparison using TOPS representations of protein structure

We describe the design and implementation of a fast topology–based method for protein structure comparison. The approach uses the TOPS topological representation of protein structure, aligning two structures using a common discovered pattern and generating measure of distance derived from an insert score. Heavy use is made of a constraint-based pattern matching algorithm for TOPS diagrams that we have designed and described elsewhere Gilbert et al. (1999). The comparison system is maintained at the European Bioinformatics Institute and is available over the Web via the at tops.ebi.ac.uk/tops. Users submit a structure description in Protein Data Bank (PDB) format and can compare it with structures in the entire PDB or a representative subset of protein domains, receiving the results by email

Gene Duplication Models and Reconstruction of Gene Regulatory Network Evolution from Network Structure

In this paper we study evolution of gene regulatory networks from the graph-theoretic perspective. We consider two gene duplication models that are based on those studied before, but are more general and/or mathematically more precise than previously published schemes. Our aims are to assess the biological appropriateness of the proposed models and to study the possibilities of reconstruction of the evolution history of networks solely on the basis of network topology. For one of the proposed models, which is fully deterministic, we provide an exact algorithm for reconstruction of evolutionary history of the network. The algorithm is applicable in real time to networks with up to 200 genes, which is comparable to sizes of real biological networks. The other proposed model involves random deletions of gene interactions. In this case a heuristic modification of the algorithm can be used to identify a large subset of genes that have been duplicated during the last duplication event. The methods have been tested for analysis of yeast gene regulatory network and have been able to identify several biologically confirmed pairs of duplicated genes. Similarity between inferred pairs of gene duplicates is shown to be above average, thus indicating that traces from gene duplications, which have occurred long time ago, can still be detected from the network topology alone.The work was supported by Latvian Council of Science grant 258/2012 and Latvian State Research programme project NexIT (2014-2017)

A comparative study of the properties of industrially produced humic substances

Humic substances (HSs) are produced industrially in large quantities from low rank coal, weathered coal, peat, also from soils, composts and other sources. Considering that the applications of industrially produced HSs also include food, pharmaceutical applications and environmental technologies, it is important to evaluate their composition and quality and to identify their sources. The aim of the present study is to compare the properties of industrially produced HS samples. HSs were characterised using spectroscopic and other methods. For the identification of origin of HSs, different methods can be used, such as elemental analysis and ratios of light stable isotopes. The results of the study indicate that many industrially produced HSs are of poor quality (low concentration of basic substance, admixture of undesirable substances, pollutants, no quality indications). In this situation, rigorous quality control should be implemented, providing detailed characteristics of the product. The composition of materials suggested for agricultural applications has not been analysed much. Most of the studied materials were designated as HAs, followed by fulvic acids (FAs) and HSs. However, an analysis of the humic matter types indicates that the majority of substances offered on the market are in fact mixtures of HAs and FAs; so, it would be more appropriate to designate them as HSs or their salts. This study identifies the main quality problems of industrially produced humic substances: 1) lack of strict quality indicators, 2) absence of indication of source materials/origins of HSs

A System for Information Management in BioMedical Studies—SIMBioMS

Summary: SIMBioMS is a web-based open source software system for managing data and information in biomedical studies. It provides a solution for the collection, storage, management and retrieval of information about research subjects and biomedical samples, as well as experimental data obtained using a range of high-throughput technologies, including gene expression, genotyping, proteomics and metabonomics. The system can easily be customized and has proven to be successful in several large-scale multi-site collaborative projects. It is compatible with emerging functional genomics data standards and provides data import and export in accepted standard formats. Protocols for transferring data to durable archives at the European Bioinformatics Institute have been implemented

Fibrinolytic system changes in liver surgery : A pilot observational study

Publisher Copyright: © 2018 Ozolina, Nemme, Ozolins, Bjertnæs, Vanags, Gardovskis, Viksna and Krumina.Introduction: Bleeding occurs frequently in liver surgery. Unbalance between tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) concentrations might increase bleeding. Our aim was to analyze perioperative fibrinolytic changes during liver surgery. Materials and Methods: We evaluated 15 patients for inclusion into a prospective pilot study of liver surgery. We assessed fibrinolysis by plasma PAI-1 and t-PA: before surgery (T1), before Pringle maneuver (PM;T2), at the end of surgery (T3) and 24 h postoperatively (T4), and registered demographic and laboratory data, extent and duration of surgery, hemodynamic parameters, blood loss, and transfused volumes of blood products. Data presented as mean ± SD. Significance at P < 0.05. Results: After exclusion of six patients only undergoing biopsies, we included six women and three men aged 49.1 ± 19.6 years; two patients with liver metastases of colorectal cancer and hepatocellular carcinoma, respectively, two with focal nodular hyperplasia, two with hepatic hemangioma, and one with angiomyolipoma. Six patients underwent PM. PAI-1 plasma concentration (n = 9) rose from 6.25 ± 2.25 at T1 through 17.30 ± 14.59 ng/ml at T2 and 28.74 ± 20.4 (p = 0.007) and 22.5 ± 16.0 ng/ml (p = 0.04), respectively, at T3 and T4. Correspondingly, t-PA plasma concentration (n = 9) increased from 4.76 ± 3.08 ng/ml at T1 through 8.00 ± 5.10 ng/ml (p = 0.012) at T2 and decreased to 4.25 ± 2.29 ng/ml and 3.04 ± 3.09 at T3 and T4, respectively. Plasma t-PA level at T2 was significantly different from those at T1, T3, and T4 (p < 0.004). In PM patients, t-PA levels increased from T1, peaked at T2 (p = 0.001), and subsequently decreased at T3 and T4 (p = 0.011 and p = 0.037), respectively. Mean blood loss was 1,377.7 ± 1,062.8 ml; seven patients received blood products. Patients with higher PAI-1 levels at T3 received more fresh frozen plasma (r = 0.79; p = 0.01) and red blood cells (r = 0.88; p = 0.002). Conclusions: During liver surgery, fibrinolysis increased, as evidenced by rises in plasma PAI-1and t-PA, especially after start of surgery and following PM. Transfused volumes of blood products correlated with higher plasma concentrations of PAI-1. Confirming this tendency requires a larger cohort of patients.publishersversionPeer reviewe

An optimized TOPS+ comparison method for enhanced TOPS models

This article has been made available through the Brunel Open Access Publishing Fund.Background Although methods based on highly abstract descriptions of protein structures, such as VAST and TOPS, can perform very fast protein structure comparison, the results can lack a high degree of biological significance. Previously we have discussed the basic mechanisms of our novel method for structure comparison based on our TOPS+ model (Topological descriptions of Protein Structures Enhanced with Ligand Information). In this paper we show how these results can be significantly improved using parameter optimization, and we call the resulting optimised TOPS+ method as advanced TOPS+ comparison method i.e. advTOPS+. Results We have developed a TOPS+ string model as an improvement to the TOPS [1-3] graph model by considering loops as secondary structure elements (SSEs) in addition to helices and strands, representing ligands as first class objects, and describing interactions between SSEs, and SSEs and ligands, by incoming and outgoing arcs, annotating SSEs with the interaction direction and type. Benchmarking results of an all-against-all pairwise comparison using a large dataset of 2,620 non-redundant structures from the PDB40 dataset [4] demonstrate the biological significance, in terms of SCOP classification at the superfamily level, of our TOPS+ comparison method. Conclusions Our advanced TOPS+ comparison shows better performance on the PDB40 dataset [4] compared to our basic TOPS+ method, giving 90 percent accuracy for SCOP alpha+beta; a 6 percent increase in accuracy compared to the TOPS and basic TOPS+ methods. It also outperforms the TOPS, basic TOPS+ and SSAP comparison methods on the Chew-Kedem dataset [5], achieving 98 percent accuracy. Software Availability: The TOPS+ comparison server is available at http://balabio.dcs.gla.ac.uk/mallika/WebTOPS/.This article is available through the Brunel Open Access Publishing Fun

Capturing, sharing and analysing biophysical data from protein engineering and protein characterization studies

Large amounts of data are being generated annually on the connection between the sequence, structure and function of proteins using site-directed mutagenesis, protein design and directed evolution techniques. These data provide the fundamental building blocks for our understanding of protein function, molecular biology and living organisms in general. However, much experimental data are never deposited in databases and is thus ‘lost’ in journal publications or in PhD theses. At the same time theoretical scientists are in need of large amounts of experimental data for benchmarking and calibrating novel predictive algorithms, and theoretical progress is therefore often hampered by the lack of suitable data to validate or disprove a theoretical assumption. We present PEAT (Protein Engineering Analysis Tool), an application that integrates data deposition, storage and analysis for researchers carrying out protein engineering projects or biophysical characterization of proteins. PEAT contains modules for DNA sequence manipulation, primer design, fitting of biophysical characterization data (enzyme kinetics, circular dichroism spectroscopy, NMR titration data, etc.), and facilitates sharing of experimental data and analyses for a typical university-based research group. PEAT is freely available to academic researchers at http://enzyme.ucd.ie/PEAT

Associations of HLA DR and DQ molecules with Lyme borreliosis in Latvian patients

Copyright: Copyright 2012 Elsevier B.V., All rights reserved.Background: Many autoimmune diseases are associated with variants of HLA genes such as those encoding the MHC complex. This correlation is not absolute, but may help in understanding of the molecular mechanism of disease. The purpose of this study was to determine HLA-DR,-DQ alleles in Latvian patients with Lyme borreliosis and control (healthy) persons. Case patients and control subjects were similar in age, gender and ethnic heritage and differed only as regards the presence of Borrelia burgdorferi infection. The study included 25 patients with clinical stage - erythema migrans and 30 control (healthy) persons. HLA genotyping was performed by PCR with sequence-specific primers. Results: The results show difference in HLA-DRB1 alleles distribution between patients and control subjects. The frequencies of HLA-DRB1 *04 (OR 11.24; p<0.007) and HLA-DRB1 *17 (03) (OR 8.05; p<0.033) were increased in the Lyme disease patients. And the frequency of allele DRB1*13 (OR 0.12; p<0.017) was lower in Borreliosis patients and higher in control group. But, significant differences in frequencies of HLA-DQ alleles we did not detect. Conclusions: HLA predisposition to Lyme borreliosis appears not to be limited to HLA molecules, but some HLA-DR alleles also have a significant influence, and, may have implications in our understanding of pathogenesis of this disease. In particular, HLA-DRB1*04 and DRB1 *17 (03) may contribute to the Lyme borreliosis development in Latvian population.publishersversionPeer reviewe