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SNVDis:A Proteome-wide Analysis Service for Evaluating nsSNVs in Protein Functional Sites and Pathways

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Genomics, Proteomics & Bioinformatics 2013年第2期11卷 122-126页

作者： Konstantinos Karagiannis vahan simonyan Raja Mazumder Department of Biochemistry and Molecular Biology George Washington University Medical Center Center for Biologics Evaluation and Research Food and Drug Administration

Amino acid changes due to non-synonymous variation are included as annotations for individual proteins in UniProtKB/Swiss-Prot and RefSeq which present biological data in a pro- tein- or gene-centric fashion. Unfortunately, proteome-wide analysis of non-synonymous single- nucleotide variations （nsSNVs） is not easy to perform because information on nsSNVs and func- tionally important sites are not well integrated both within and between databases and their search engines. We have developed SNVDis that allows evaluation of proteome-wide nsSNV distribution in functional sites, domains and pathways. More specifically, we have integrated human-specific data from major variation databases （UniProtKB, dbSNP and COSMIC）, comprehensive sequence feature annotation from UniProtKB, Pfam, RefSeq, Conserved Domain Database （CDD） and pathway information from Protein ANalysis THrough Evolutionary Relationships （PANTHER） and mapped all of them in a uniform and comprehensive way to the human reference proteome pro- vided by UniProtKB/Swiss-Prot. Integrated information of active sites, pathways, binding sites, domains, which are extracted from a number of different sources, provides a detailed overview of how nsSNVs are distributed over the human proteome and pathways and how they intersect with functional sites of proteins. Additionally, it is possible to find out whether there is an over- or under-representation of nsSNVs in specific domains, pathways or user-defined protein lists. The underlying datasets are updated once every 3 months. SNVDis is freely available at http：//***- ***/tool/snvdis.

关键词： Active site Binding site N-linked glycosylation nsSNP nsSNV Variation

Structure-based Comparative Analysis and Prediction of N-linked Glycosylation Sites in Evolutionarily Distant Eukaryotes

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Genomics, Proteomics & Bioinformatics 2013年第2期11卷 96-104页

作者： Phuc Vinh Nguyen Lam Radoslav Goldman Konstantinos Karagiannis Tejas Narsule vahan simonyan Valerii Soika Raja Mazumder Life Sciences Department Paris Diderot University Department of Biochemistry and Molecular Biology George Washington University Medical Center Department of Oncology Georgetown University Center for Biologics Evaluation and Research Food and Drug Administration

The asparagine-X-serine/threonine （NXS/T） motif, where X is any amino acid except proline, is the consensus motif for N-linked glycosylation. Significant numbers of high-resolution crystal structures of glycosylated proteins allow us to carry out structural analysis of the N-linked glycosylation sites （NGS）. Our analysis shows that there is enough structural information from diverse glycoproteins to allow the development of rules which can be used to predict NGS. A Python-based tool was developed to investigate asparagines implicated in N-glycosylation in five species： Homo sapiens, Mus musculus, Drosophila melanogaster, Arabidopsis thaliana and Saccharo- myees cerevisiae. Our analysis shows that 78 % of all asparagines of NXS/T motif involved in N-gly- cosylation are localized in the loop/turn conformation in the human proteome. Similar distribution was revealed for all the other species examined. Comparative analysis of the occurrence of NXS/T motifs not known to be glycosylated and their reverse sequence （S/TXN） shows a similar distribu- tion across the secondary structural elements, indicating that the NXS/T motif in itself is not bio- logically relevant. Based on our analysis, we have defined rules to determine NGS. Using machine learning methods based on these rules we can predict with 93% accuracy if a particular site will be glycosylated. If structural information is not available the tool uses structural prediction results resulting in 74% accuracy. The tool was used to identify glycosylation sites in 108 human proteins with structures and 2247 proteins without structures that have acquired NXS/T site/s due to non-synonymous variation. The tool, Structure Feature Analysis Tool （SFAT）, is freely available to the public at http：//***/tools/sfat.

关键词： N-linked glycosylation Gain and loss of glycosyla-tion nsSNP nsSNV Variation

Internal Electrical Noises of BioFET Sensors Based on Various Architectures

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Open Journal of Biophysics 2021年第2期11卷 177-204页

作者： Lusine Gasparyan Ferdinand Gasparyan vahan simonyan Yerevan State University Yerevan Armenia DNA-HIVE LLC Rockville MD USA

The results of a comparative literature analysis of internal electrical noises and signal-to-noise ratio for nanoscale BioFET (biological field-effect transistor) and DNA (deoxyribonucleic acid) sensors based on different architectures MIS (metal-insulator-semiconductor), EIS (electrolyte-insulator-semi-conductor) and ISFET (ion-selective field-effect transistor) are presented. Main types, models and mechanisms of internal noises of bio- & chemical field-effect based sensors are analyzed, summarized and presented. For the first time, corresponding detail electrical equivalent circuits were built to calculate the spectral densities of noises generated in the active part of a solid (semiconductor, dielectric) and in an aqueous solution for MIS, EIS and ISFET structures based sensors. Complete expressions are obtained for the rms (root mean square) value of the noise current (or voltage), as well as the noise spectral densities for the architectures under study. The miniaturization of biosensors leads to a decrease in the level of the useful signal-current. For successful operation of the sensor, it is necessary to ensure a high value of the SNR (signal-to-noise ratio). In case of weak useful signals, it is necessary to reduce the level of internal electrical noise. This work is devoted to a detailed study of the types and mechanisms of internal electrical noises in specific biosensor architectures.

关键词： Noise Sensor BioFET Signal-to-Noise Ratio

ISFET Based DNA Sensor: Current-Voltage Characteristic and Sensitivity to DNA Molecules

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Open Journal of Biophysics 2019年第4期9卷 239-253页

作者： Lusine Gasparyan Ilya Mazo vahan simonyan Ferdinand Gasparyan Argentis LLC Gaithersburg MD USA Yerevan State University Yerevan Armenia The Department of Biochemistry & Molecular Medicine The George Washington University Washington DC USA

Dependency of both source-drain current and current sensitivity of nanosize ISFET biosensor vs. concentration of DNA molecules in aqueous solution theoretically is investigated. In calculations it is carried out effects concerning charge carriers distribution in current channel and concerning carriers’ mobility behavior in high electrical fields in the channel. The influence of DNA molecules on the work of ISFET biosensors is manifested by a change in the magnitude of the gate surface charge. Starting with fairly low concentrations of DNA, ISFET sensors respond to the presence of DNA molecules in an aqueous solution which is manifested by modulation of channel conductance and therefore the source-drain current changes of the field-effect transistor. It is shown that the current sensitivity with respect to concentration of DNA molecules linearly depends on the source-drain voltage and reaches high values.

关键词： DNA ISFET Sensitivity Nanosize Current Channel

DNA Sequencing Modified Method through Effective Regulation of Its Translocation Speed in Aqueous Solution

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Open Journal of Biophysics 2020年第2期10卷 96-112页

作者： Lusine Gasparyan Ilya Mazo Ferdinand Gasparyan vahan simonyan Yerevan State University Yerevan Armenia DNA-HIVE LLC 15313 Diamond Cove Terrace Rockville MD USA Argentis LLC Gaithersburg MD USA

Solid-state nanopore DNA sequencing modified method is developed. Method is based on the tunnel current investigation through the nanogap made on lateral gold electrodes in the form of nanowires or nanoribbons. The movement of DNA in aqueous solution is regulated by the potential applied to reference electrode. The potential applied to the lateral metal electrodes helps to the creation of the molecular junctions. They consist of the nucleosides passing through the pores. Taking into account that DNA moves under gravity, electrophoretic and drag forces, the analytic expression for the DNA translocation speed is calculated and analyzed. The conditions for decreasing the DNA translocation speed or increasing the nucleosides reading time are received. It is shown that one can control value of the DNA molecules bases reading time and the frequency of the bases passes by the choice of magnitude of the potential applied to reference electrode. Our results, therefore potentially suggest a realistic, inherently design-specific, high-throughput nanopore DNA sequencing device/cell as a de-novo alternative to the existing methods.

关键词： DNA Sequencing DNA Speed Forces Reading Time

Noises and Signal-to-Noise Ratio of Nanosize EIS and ISFET Biosensors

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Open Journal of Biophysics 2020年第1期10卷 1-12页

作者： Lusine Gasparyan Ilya Mazo vahan simonyan Ferdinand Gasparyan DNA-HIVE LLC 15313 Diamond Cove Terrace Rockville USA Yerevan State University Yerevan Armenia Argentis LLC Gaithersburg USA

The results of comparative theoretical analyzes of the behavior of internal low-frequency noises, signal-to-noise ratio and sensitivity to DNA molecules for EIS and ISFET based nanosize biosensors are presented. It is shown that EIS biosensor is more sensitive to the presence of DNA molecules in aqueous solution than ISFET sensor. Internal electrical noises level decreases with the increase of concentration of DNA molecules in aqueous solution. In the frequency range 10−3 - 103 Hz noises level for EIS sensor about in three orders is higher than for ISFET sensor. In the other hand, signal-to-noise ratio for capacitive EIS biosensor is much higher than for ISFET sensor.

关键词： Biosensor Noise Sensitivity Signal-to-Noise Ratio

DNA Sequencing: Current State and Prospects of Development

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Open Journal of Biophysics 2019年第3期9卷 169-197页

作者： Lusine Gasparyan Ilya Mazo vahan simonyan Ferdinand Gasparyan Argentys Informatics LLC Gaithersburg MD USA Yerevan State University Yerevan Armenia The Department of Biochemistry & Molecular Medicine The School of Medicine and Health Sciences The George Washington University Washington DC USA

In this review, we collected and classified the stages of development of DNA sequencing methods and described its peculiarities. We pay attention mostly on solid-stead nanopore sequencing methods. Detailed discussion of the peculiarity and feasibility of the electrical methods of DNA sequencing is discussed. The detail analyses of the literature data, some critical considerations and the potential ways of optimization of DNA nanopore sequencing were presented.

关键词： DNA Sequencing ISFET Sensor EIS Sensor Solid-Stead Nanopore

Non-Invasive Approach to Early Diagnosis of the Formation of Oncological Neoplasms

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Journal of Cancer Therapy 2023年第4期14卷 202-210页

作者： Rafik Sargsyan Gagik Karamyan Luiza simonyan Armen Manukyan Vahram Sargsyan LA Orbeli Institute of Physiology of the National Academy of Sciences of Armenia Erevan USA

The currently developed instrumental approaches for detecting pathological changes in the body have a number of disadvantages. The most important of them is that the equipment is sensitive to the detection of diseases only from a certain threshold level of destructive changes in the body. The present article discusses the possibility of using the new instrumental complex “Bioscope” for early and non-invasive diagnosis of the beginning of the formation of ontological neoplasm’s in the body.

关键词： Cancer Early Non-Invasive Diagnostic Bioscope

Left atrial appendage occluder implantation for stroke prevention in elderly patients with atrial fibrillation： acute and long-term results

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Journal of Geriatric Cardiology 2017年第9期14卷 590-592页

作者： Karapet V Davtyan Andrey A Kalemberg Arpi H Topchyan Georgiy Y simonyan Ekaterina V Bazaeva Victoria S Shatahtsyan Laboratory for Interventional Arrhythmia Treatment of “National Medical Research Center for Preventive Medicine” Ministry of Healthcare of the RussianFederation Petroverigskiy lane Moscow Russia

Atrial fibrillation （AF） is the most common cardiac ar-rhythmia in clinical practice with an increasing incidenceand prevalence. With ageing, the risk of thromboembolicand hemorrhagic events increases dramatically. As it hasbeen reported previously, 3-year survival rate among pa-tients with AF over 75 years of age after stroke is less than50%, and almost 90% of those patients will remain dis-abled.

关键词： Left atrial appendage closure Oral anticoagulation therapy Stroke prevention The elderly