PHOG-BLAST – a new generation tool for fast similarity search of protein families

BACKGROUND: The need to compare protein profiles frequently arises in various protein research areas: comparison of protein families, domain searches, resolution of orthology and paralogy. The existing fast algorithms can only compare a protein sequence with a protein sequence and a profile with a sequence. Algorithms to compare profiles use dynamic programming and complex scoring functions. RESULTS: We developed a new algorithm called PHOG-BLAST for fast similarity search of profiles. This algorithm uses profile discretization to convert a profile to a finite alphabet and utilizes hashing for fast search. To determine the optimal alphabet, we analyzed columns in reliable multiple alignments and obtained column clusters in the 20-dimensional profile space by applying a special clustering procedure. We show that the clustering procedure works best if its parameters are chosen so that 20 profile clusters are obtained which can be interpreted as ancestral amino acid residues. With these clusters, only less than 2% of columns in multiple alignments are out of clusters. We tested the performance of PHOG-BLAST vs. PSI-BLAST on three well-known databases of multiple alignments: COG, PFAM and BALIBASE. On the COG database both algorithms showed the same performance, on PFAM and BALIBASE PHOG-BLAST was much superior to PSI-BLAST. PHOG-BLAST required 10–20 times less computer memory and computation time than PSI-BLAST. CONCLUSION: Since PHOG-BLAST can compare multiple alignments of protein families, it can be used in different areas of comparative proteomics and protein evolution. For example, PHOG-BLAST helped to build the PHOG database of phylogenetic orthologous groups. An essential step in building this database was comparing protein complements of different species and orthologous groups of different taxons on a personal computer in reasonable time. When it is applied to detect weak similarity between protein families, PHOG-BLAST is less precise than rigorous profile-profile comparison method, though it runs much faster and can be used as a hit pre-selecting tool

PHOG: a database of supergenomes built from proteome complements

BACKGROUND: Orthologs and paralogs are widely used terms in modern comparative genomics. Existing procedures for resolving orthologous/paralogous relationships are often based on manual revision of clusters of orthologous groups and/or lack any rigorous evolutionary base. DESCRIPTION: We developed a completely automated procedure that creates clusters of orthologous groups at each node of the taxonomy tree (PHOGs – Phylogenetic Orthologous Groups). As a result of this procedure, a tree of orthologous groups was obtained. Each cluster is a "supergene" and it is represented by an "ancestral" sequence obtained from the multiple alignment of orthologous and paralogous genes. The procedure has been applied to the taxonomy tree of organisms from all three domains of life. Protein complements from 50 bacterial, archaeal and eukaryotic species were used to create PHOGs at all tree nodes. 51367 PHOGs were obtained at the root node. CONCLUSION: The PHOG database demonstrates that it is possible to automatically process any number of sequenced genomes and to reconstruct orthologous and paralogous relationships between genomes using a rigorous evolutionary approach. This database can become a very useful tool in various areas of comparative genomics

Positron annihilation spectroscopy of vacancy-type defects hierarchy in submicrocrystalline nickel during annealing

Positron annihilation and X-ray diffraction analysis have been used to study submicrocrystalline nickel samples prepared by equal channel angular pressing. In the as-prepared samples the positrons are trapped at dislocation-type defects and in vacancy clusters that can include up to 5 vacancies. The study has revealed that the main positron trap centers at the annealing temperature of deltaT= 20°C-180°C are low-angle boundaries enriched by impurities. At deltaT = 180°C-360°C, the trap centers are low-angle boundaries providing the grain growth due to recrystallization in-situ

An automated stochastic approach to the identification of the protein specificity determinants and functional subfamilies

<p>Abstract</p> <p>Background</p> <p>Recent progress in sequencing and 3 D structure determination techniques stimulated development of approaches aimed at more precise annotation of proteins, that is, prediction of exact specificity to a ligand or, more broadly, to a binding partner of any kind.</p> <p>Results</p> <p>We present a method, SDPclust, for identification of protein functional subfamilies coupled with prediction of specificity-determining positions (SDPs). SDPclust predicts specificity in a phylogeny-independent stochastic manner, which allows for the correct identification of the specificity for proteins that are separated on a phylogenetic tree, but still bind the same ligand. SDPclust is implemented as a Web-server <url>http://bioinf.fbb.msu.ru/SDPfoxWeb/</url> and a stand-alone Java application available from the website.</p> <p>Conclusions</p> <p>SDPclust performs a simultaneous identification of specificity determinants and specificity groups in a statistically robust and phylogeny-independent manner.</p

RegTransBase—a database of regulatory sequences and interactions in a wide range of prokaryotic genomes

RegTransBase is a manually curated database of regulatory interactions in prokaryotes that captures the knowledge in public scientific literature using a controlled vocabulary. Although several databases describing interactions between regulatory proteins and their binding sites are already being maintained, they either focus mostly on the model organisms Escherichia coli and Bacillus subtilis or are entirely computationally derived. RegTransBase describes a large number of regulatory interactions reported in many organisms and contains the following types of experimental data: the activation or repression of transcription by an identified direct regulator, determining the transcriptional regulatory function of a protein (or RNA) directly binding to DNA (RNA), mapping or prediction of a binding site for a regulatory protein and characterization of regulatory mutations. Currently, RegTransBase content is derived from about 3000 relevant articles describing over 7000 experiments in relation to 128 microbes. It contains data on the regulation of about 7500 genes and evidence for 6500 interactions with 650 regulators. RegTransBase also contains manually created position weight matrices (PWM) that can be used to identify candidate regulatory sites in over 60 species. RegTransBase is available at

Кремниевая электронно-чувствительная pin-линейка, облучаемая с обратной стороны

Introduction. In recent decades, in the field of photoelectronics, special attention has been paid to the development of semiconductor matrix photodetectors. These detectors have become an effective alternative to existing television receiving systems. Among such devices, linear position-sensitive sensors are used in cases where the rapid registration of changes to the environment is required (for instance, high-speed locators for flying vehicles).Aim. To develop a strip of silicon pin-diodes as part of a hybrid IR-detector for effective registration of photoelectrons with time resolution less than 10 ns, as well as to model the key electro-physical characteristics of the strip.Materials and methods. In the device under development, the registration of photoelectrons is achieved by the presence of a near-surface field using p ++–p junction formed by diffusion of boron into the silicon with resistivity of 3 kΩ · cm. The pulling field is also formed in the space charge region between p ++ - and n ++ -regions. Diffusion of phosphorus was carried out to create the n ++ -region. Numerical calculations of potential distribution, concentration of free charge carriers and currents were carried out using software for 1D- and 2D-modelling (SimWin and TCAD Synopsys).Results. 2D-calculation of charge carrier concentration and potential distribution was performed. The study determined the minimum bias for the complete depletion of the i-layer, including that for longitudinal grooves of various depths. The strip was tested as part of a hybrid photoelectric device by irradiating light pulses from IR LED. When the voltage on the diodes was reached –270 V, the duration of the signal front on all channels was 5…9 ns.Conclusion. For use in IR-hybrid detectors, a strip of 12 silicon pin-diodes was developed with a sensitive element of 24 × 0.2 mm in dimension. The study of pulse characteristics showed that the necessary duration of the front signal on all channels was achieved without thinning thus satisfying the requirements for high-speed position-sensitive sensor of the infrared radiation.Введение. В последние десятилетия в фотоэлектронике особое внимание уделяется разработке полупроводниковых матричных фотоприемных устройств, которые фактически стали эффективной альтернативой существующим аналоговым телевизионным приемным системам. Среди таких устройств линейные позиционно-чувствительные датчики применяются для регистрации быстрых изменений в окружающей обстановке и их последующей обработки (например, быстродействующие локаторы летательных аппаратов).Цель работы. Создание линейки кремниевых pin-диодов для использования в составе гибридного детектора ИК-излучения с целью регистрации фотоэлектронов с временны́м разрешением лучше 10 нс. Моделирование основных электрофизических характеристик линейки.Материалы и методы. В разрабатываемом приборе регистрация фотоэлектронов обеспечивается за счет наличия приповерхностного поля при использовании p ++–p-перехода, сформированного диффузией бора в кремний с удельным сопротивлением 3 кОм · см. Тянущее поле, в свою очередь, также формируется в области объемного заряда между p ++ - и n ++ -областями. Для создания n ++ -области проводилась диффузия фосфора. Численные расчеты распределения потенциала, концентрации свободных носителей заряда и токов проводились в программных пакетах одномерного (SimWin) и двумерного (TCAD Synopsys) моделирования.Результаты. Проведен двумерный расчет распределения концентрации свободных носителей заряда и потенциала в исследуемой pin-структуре. Определены минимальные напряжения, обеспечивающие полное обеднение i-слоя, в том числе для случая продольной канавки различной глубины. Линейка тестировалась в составе гибридного фотоэлектронного прибора облучением световыми импульсами от ИК-светодиода. При напряжении на диодах линейки –270 В достигнута длительность фронта сигнала на всех каналах 5...9 нс.Заключение. Для гибридного детектора ИК-излучения разработана линейка из 12 кремниевых pin-диодов, с размерами чувствительной области элемента 24 × 0.2 мм. По результатам исследований импульсной характеристики показано, что без операции утонения достигнута длительность фронта сигнала на всех каналах, удовлетворяющая требованиям к быстродействующему позиционно-чувствительному датчику ИК-излучения