МЕТОДИ КЛАСТЕРИЗАЦІЇ В ПРОГРАМІ MICROARRAYTOOL ДЛЯ АНАЛІЗУ ДАНИХ ДНК-МІКРОАРРЕЇВ

Microarray technologies (DNA chips) allow to perform a quantitative analysis of expression of ten thousands genes. In this work a novel Microarraytool program was developed which allows to perform the cluster analysis and to compare the different experiments data by statistical analysis. Several clustering algorithms have been implemented into Microarraytool program: hierarchical clustering, k-means clustering, self-organizing maps (SOM) algorithm and self-organizing tree maps (SOTA) algorithm. The testing of these algorithms was performed using the Stanford Microarray Database for expression of 8613 individual genes in human fibroblasts after stimulation. The testing procedure revealed a correct performance of these algorithms implemented into Microarraytool program.Микроаррей-технологии или ДНК-чипы позволяют проводить количественный анализ экспрессии десятков тысяч генов. В данной работе описана новая программа Microarraytool для анализа ДНК микроаррей-данных, которая позволяет проводить трансформацию и нормализацию данных, выполнять кластерный анализ и сравнивать разные эксперименты с помощью статистического анализа. В программе имплементированы такие методы кластерного анализа: иерархический кластерний анализ, метод кластеризации k-средних, карты самоорганизующихся признаков (SOM) и SOTA- кластеризация. Проведено тестирование алгоритмов кластерного анализа для микроаррей-данных Стэнфордской базы данных по экспрессии первичных фибробластов человека для 8613 индивидуальных генов на разных временных промежутках после стимуляции. Анализ данных показал корректное выполнение алгоритмов, имплементированных в программе Microarraytool.Мікроаррей-технології або ДНК-чіпи дозволяють проводити кількісний аналіз експресії десятків тисяч генів. В даній роботі описана нова програма Microarraytool для аналізу ДНК мікроаррей-даних, яка дозволяє проводити трансформацію та нормалізацію даних, виконувати кластерний аналіз та порівнювати різні експерименти за допомогою статистичного аналізу. Імплементовано такі методи кластерного аналізу: ієрархічний кластерний аналіз, метод кластеризації k-середніх, карти ознак, що самоорганізуються (SOM) та SOTA-кластеризація. Проведено тестування алгоритмів для кластерного аналізу для мікроаррей-даних Стенфордської бази даних з експресії первинних фібробластів людини для 8613 індивідуальних генів на різних часових проміжках після стимуляції. Аналіз даних показав коректне виконання алгоритмів, імплементованих в програмі Microarraytool

Whole-genome sequencing provides new insights into the clonal architecture of Barrett's esophagus and esophageal adenocarcinoma.

The molecular genetic relationship between esophageal adenocarcinoma (EAC) and its precursor lesion, Barrett's esophagus, is poorly understood. Using whole-genome sequencing on 23 paired Barrett's esophagus and EAC samples, together with one in-depth Barrett's esophagus case study sampled over time and space, we have provided the following new insights: (i) Barrett's esophagus is polyclonal and highly mutated even in the absence of dysplasia; (ii) when cancer develops, copy number increases and heterogeneity persists such that the spectrum of mutations often shows surprisingly little overlap between EAC and adjacent Barrett's esophagus; and (iii) despite differences in specific coding mutations, the mutational context suggests a common causative insult underlying these two conditions. From a clinical perspective, the histopathological assessment of dysplasia appears to be a poor reflection of the molecular disarray within the Barrett's epithelium, and a molecular Cytosponge technique overcomes sampling bias and has the capacity to reflect the entire clonal architecture

The first experience of application of robotic systems for stereotactic hypofractionated radiotherapy "CyberKnife" in the treatment of patients with renal cell cancer

Presents the first experience of application of stereotactic RA-diotherapy on the robotic system 'CyberKnife* in the establishment of health care Chelyabinsk Regional Clinical Oncological Dispensary in patients with renal cell cancer. Treatment received 2 patients with renal cell carcinoma, and one patient carried out the irradiation of both kidneys. As a result, the first patient received a com-plete tumor resorption of the right kidney and reducing the size and lowering the contrast of the tumor of the left kidney. Kidney function is not deteriorated. The second patient has decreased the tumor size, but retains the contrast in the vascular phase. The function of a single kidney is not deteriorated.Представлен первый опыт применения стереотаксической радиотерапии на роботизированной системе «CyberKnife» в ГБУЗ «Челябинский Областной Клинический Онкологический Диспансер» у больных почечно-клеточным раком. Лечение получили 2 пациента с почечно-клеточным раком, причем у одного пациента проведено облучение обеих почек. В результате у первого пациента получена полная резорбция опухоли правой почки и уменьшение размеров и снижение контрастирования опухоли левой почки. Функция почек не ухудшилась. У второго пациента уменьшились размеры опухоли, но сохраняется контрастирование в сосудистые фазы. Функция единственной почки не ухудшилась

Charting the NF-κB Pathway Interactome Map

Inflammation is part of a complex physiological response to harmful stimuli and pathogenic stress. The five components of the Nuclear Factor κB (NF-κB) family are prominent mediators of inflammation, acting as key transcriptional regulators of hundreds of genes. Several signaling pathways activated by diverse stimuli converge on NF-κB activation, resulting in a regulatory system characterized by high complexity. It is increasingly recognized that the number of components that impinges upon phenotypic outcomes of signal transduction pathways may be higher than those taken into consideration from canonical pathway representations. Scope of the present analysis is to provide a wider, systemic picture of the NF-κB signaling system. Data from different sources such as literature, functional enrichment web resources, protein-protein interaction and pathway databases have been gathered, curated, integrated and analyzed in order to reconstruct a single, comprehensive picture of the proteins that interact with, and participate to the NF-κB activation system. Such a reconstruction shows that the NF-κB interactome is substantially different in quantity and quality of components with respect to canonical representations. The analysis highlights that several neglected but topologically central proteins may play a role in the activation of NF-κB mediated responses. Moreover the interactome structure fits with the characteristics of a bow tie architecture. This interactome is intended as an open network resource available for further development, refinement and analysis

Parsimonious Higher-Order Hidden Markov Models for Improved Array-CGH Analysis with Applications to Arabidopsis thaliana

Array-based comparative genomic hybridization (Array-CGH) is an important technology in molecular biology for the detection of DNA copy number polymorphisms between closely related genomes. Hidden Markov Models (HMMs) are popular tools for the analysis of Array-CGH data, but current methods are only based on first-order HMMs having constrained abilities to model spatial dependencies between measurements of closely adjacent chromosomal regions. Here, we develop parsimonious higher-order HMMs enabling the interpolation between a mixture model ignoring spatial dependencies and a higher-order HMM exhaustively modeling spatial dependencies. We apply parsimonious higher-order HMMs to the analysis of Array-CGH data of the accessions C24 and Col-0 of the model plant Arabidopsis thaliana. We compare these models against first-order HMMs and other existing methods using a reference of known deletions and sequence deviations. We find that parsimonious higher-order HMMs clearly improve the identification of these polymorphisms. Moreover, we perform a functional analysis of identified polymorphisms revealing novel details of genomic differences between C24 and Col-0. Additional model evaluations are done on widely considered Array-CGH data of human cell lines indicating that parsimonious HMMs are also well-suited for the analysis of non-plant specific data. All these results indicate that parsimonious higher-order HMMs are useful for Array-CGH analyses. An implementation of parsimonious higher-order HMMs is available as part of the open source Java library Jstacs (www.jstacs.de/index.php/PHHMM)

Electronic Phase Shifting in Multipulse Rectifier

This paper presents a novel converter which can reduce the harmonics like the conventional multipulse converters with input three phase transformer. To reduce total harmonic distortion of input current and improve the weight and size of converters, it is suggested to use multi-pulse rectifiers with an electronic phase shift. The basic module is a 6-pulse rectifier on fully controlled switches with the reverse blocking ability. Switching frequency either coincides or is twice the power frequency. The proposed solutions allow refusing from the electromagnetic phase-shifting devices (power transformers or auto-transformers) and thereby significantly reduce the weight of the device. Unlike power factor correction systems with high-frequency modulation, the proposed converters are significantly different, as they have better electromagnetic compatibility and the virtual absence of dynamic switching losses of power switches

СИСТЕМА ЕЛЕКТРОПОСТАЧАННЯ КОНТАКТНОЇ МЕРЕЖІ ПОСТІЙНОГО СТРУМУ ІЗ ПОЗДОВЖНЬОЮ ЛІНІЄЮ ПІДВИЩЕННОЇ НАПРУГИ

The power supply system of a contact network using a longitudinal line with points of communication without transformer is considered. The approach allowing to facilitate power filters and the way of switching of in-series connected semiconductor switches with fixing a voltage on them are offered.Рассматривается система питания контактной сети, использующая продольную линию с бестрансформаторными пунктами связи. Предлагается решение, позволяющее облегчить силовые фильтры, и способ коммутации последовательно соединенных полупроводниковых ключей с фиксацией напряжения на них.Розглядається система живлення контактної мережі, що використовує поздовжню лінію з безтрансформаторними пунктами зв’язку. Пропонується спосіб керування, що дозволяє полегшити силові фільтри, й спосіб комутації послідовно з’єднаних напівпровідникових ключів з фіксацією напруги на них