<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.3 20210610//EN" "JATS-journalpublishing1-3.dtd">
<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">biopreparat</journal-id><journal-title-group><journal-title xml:lang="ru">БИОпрепараты. Профилактика, диагностика, лечение</journal-title><trans-title-group xml:lang="en"><trans-title>Biological Products. Prevention, Diagnosis, Treatment</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2221-996X</issn><issn pub-type="epub">2619-1156</issn><publisher><publisher-name>Scientific Centre for Expert Evaluation of Medicinal Products</publisher-name></publisher></journal-meta><article-meta><article-id custom-type="elpub" pub-id-type="custom">biopreparat-56</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ОБЗОРЫ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>REVIEWS</subject></subj-group></article-categories><title-group><article-title>Проблемы генотипирования микроорганизмов</article-title><trans-title-group xml:lang="en"><trans-title>Genotyping problems of microorganisms</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Волкова</surname><given-names>Р. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Volkova</surname><given-names>R. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Начальник лаборатории молекулярно-биологических и генетических методов испытаний, д-р биол. наук</p></bio><bio xml:lang="en"><p>Head of the Laboratory of molecular biology and genetic testing methods. Doctor of Biological Sciences</p></bio><email xlink:type="simple">volkova@expmed.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Сколотнева</surname><given-names>Е. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Skolotneva</surname><given-names>E. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Научный сотрудник, канд. биол. наук</p></bio><bio xml:lang="en"><p>Researcher. Candidate of Biological Sciences</p></bio><email xlink:type="simple">noemail@neicon.ru</email><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Эльберт</surname><given-names>Е. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Elbert</surname><given-names>E. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Ведущий эксперт лаборатории молекулярно-биологических и генетических методов испытаний, канд. биол. наук</p></bio><bio xml:lang="en"><p>Leading expert of the Laboratory of molecular biology and genetic testing methods. Candidate of Biological Sciences</p></bio><email xlink:type="simple">noemail@neicon.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Мыца</surname><given-names>Е. Д.</given-names></name><name name-style="western" xml:lang="en"><surname>Mytsa</surname><given-names>E. D.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Эксперт 2-й категории лаборатории молекулярно-биологических и генетических методов испытаний</p></bio><bio xml:lang="en"><p>2nd professional category expert of the Laboratory of molecular biology and genetic testing method</p></bio><email xlink:type="simple">noemail@neicon.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Давыдов</surname><given-names>Д. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Davydov</surname><given-names>D. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Начальник лаборатории бактериофагов и препаратов нормофлоры с коллекцией микроорганизмов, канд. биол. наук</p></bio><bio xml:lang="en"><p>Head of the Laboratory of bacteriophages, probiotics and culture collection. Candidate of Biological Sciences</p></bio><email xlink:type="simple">noemail@neicon.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Мовсесянц</surname><given-names>А. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Movsesyants</surname><given-names>A. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Начальник Испытательного Центра экспертизы качества МИБП, д-р мед. наук, профессор</p></bio><bio xml:lang="en"><p>Head of Test Center for Quality Expertise of medical immunobiological preparations. Doctor of Medical Sciences, professor</p></bio><email xlink:type="simple">noemail@neicon.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Меркулов</surname><given-names>В. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Merkulov</surname><given-names>V. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Заместитель генерального директора по экспертизе лекарственных средств, д-р мед. наук, профессор</p></bio><bio xml:lang="en"><p>Deputy Director-General for the expertise of drugs. Doctor of Medical Sciences, professor</p></bio><email xlink:type="simple">noemail@neicon.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Бондарев</surname><given-names>В. П.</given-names></name><name name-style="western" xml:lang="en"><surname>Bondarev</surname><given-names>V. P.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Директор Центра экспертизы и контроля МИБП, д-р мед. наук, профессор</p></bio><bio xml:lang="en"><p>Director of Center for examination and control of medical immunobiological preparations. Doctor of Medical Sciences, professor</p></bio><email xlink:type="simple">noemail@neicon.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Борисевич</surname><given-names>И. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Borisevich</surname><given-names>I. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Директор Центра планирования и координации НИР, д-р мед. наук, профессор</p></bio><bio xml:lang="en"><p>Director of Center for the planning and coordination of scientific research. Doctor of Medical Sciences, professor</p></bio><email xlink:type="simple">noemail@neicon.ru</email><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Научный центр экспертизы средств медицинского применения</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Scientific Center for Expert Evaluation of Medicinal Products</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>Московский государственный университет им. М. В. Ломоносова, биологический факультет</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Moscow Lomonosov State University, Biological faculty</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2016</year></pub-date><pub-date pub-type="epub"><day>20</day><month>02</month><year>2018</year></pub-date><volume>16</volume><issue>3</issue><fpage>139</fpage><lpage>144</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Волкова Р.А., Сколотнева Е.С., Эльберт Е.В., Мыца Е.Д., Давыдов Д.С., Мовсесянц А.А., Меркулов В.А., Бондарев В.П., Борисевич И.В., 2018</copyright-statement><copyright-year>2018</copyright-year><copyright-holder xml:lang="ru">Волкова Р.А., Сколотнева Е.С., Эльберт Е.В., Мыца Е.Д., Давыдов Д.С., Мовсесянц А.А., Меркулов В.А., Бондарев В.П., Борисевич И.В.</copyright-holder><copyright-holder xml:lang="en">Volkova R.A., Skolotneva E.S., Elbert E.V., Mytsa E.D., Davydov D.S., Movsesyants A.A., Merkulov V.A., Bondarev V.P., Borisevich I.V.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.biopreparations.ru/jour/article/view/56">https://www.biopreparations.ru/jour/article/view/56</self-uri><abstract><p>Успешность генотипирования микроорганизмов зависит от разрешающей способности метода, которая в свою очередь зависит от выбора наиболее информативного участка генома, используемых ферментов и праймеров, а также условий рестрикции генома и ПЦР амплификации. Методы анализа быстро эволюционирующих маркеров, для методов MST, MLVA, DGE, HRM, обычно, обладают большей дифференцирующей способностью, чем те, которые опираются на слабо эволюционирующие маркеры (метод MLST). Степень разрешения выше у методов типирования, зависящих от предварительной информации о ДНК матрице (PFGE, AFLP, RFLP, ДНК микрочипы), по сравнению с методами, в которых аналитические мишени ограничиваются определенными локусами (риботипирование, RFLP-PCR). Мониторинг локальных вспышек эпидемий может осуществляться при использовании быстро эволюционирующих маркеров такими методами, как RAPD-PCR, MST, или MLVA, DGE, HRM. Для длительных эпидемиологических наблюдений или популяционных исследований более пригодны маркеры консервативных участков и стабильно воспроизводимые методы (MLST, PFGE, риботипирование), а также секвенированиие полноразмерного генома. Для генотипирования микроорганизмов из полимикробных образцов целесообразно использование методов, специфичных к искомой матрице (PCR-RFLP, MLVA, DGE, HRM, MLST, MST, ДНК микрочипы). При установлении вида для полимикробных образцов оптимальным решением является изучение метагенома: совокупности генома определенного экологического сообщества бактерий. В этом случае предпочтительным является анализ высоко консервативных последовательностей ДНК, подобно гену 16S рРНК. Успехи генотипирования бактериальных штаммов позволяют исследовать взаимосвязь между генотипом и фенотипом путем филогенетического анализа генетических дистанций между штаммами в нескольких поколениях, что важно для характеристик, значимых с точки зрения эпидемиологии (вирулентностью, устойчивостью к антибиотикам и другими). Разработаны компьютизированные методы соотнесения фенотипических профилей с отсеквенированными последовательностями генома. Полногеномное секвенирование является оптимальной методикой типирования штаммов, однако высокая стоимость и необходимость использования достаточно большого количества очищенной ДНК матрицы пока ограничивает его применение.</p></abstract><trans-abstract xml:lang="en"><p>Genotyping efficiency depends on resolution of methods which provided by the target sequence of genome, efficiency of enzymes, primers and conditions of DNA restriction and PCR amplification. The most differential tools are methods involving the high evolutionary markers. They are methods MST, MLVA, DGE, HRM against to the method MLST based on the slow evolutionary marker. Methods PFGE, AFLP, DNA chips exploit the preliminary information of genome and have the better resolution than ribotyping and RFLP-PCR limited by certain loci. Monitoring of local outbreaks may be carried out using a rapidly evolving markers (methods RAPD-PCR, MST, or MLVA, DGE, HRM). The most suitable methods for prolongated epidemiological or population researches are MLST, PFGE, ribotyping and pyrosequencing analysis. Polymicrobial samples are investigated with DNA specific methods PCR-RFLP, MLVA, DGE, HRM, MLST, MST, DNA chips. The metagenomic analysis is the most informative to identify the species of bacterium from the polymicrobial sample. It is essential to use the conservative DNA sequences, for example 16S rRNA. The modern genotyping assays provide the informative and technological platform for phylogenetic studies of bacterial strains even through the several generations. The important results are figures of genetic distances between strains involving in complex of epidemiological characteristics: virulence, antibiotic resistance and the others. The computing tools for integration the phenotyping and sequencing data have developed. Whole-genome sequencing is the optimal method for bacterial genotyping. But there are several crucial restrictions of this method. It is still rather expensive and needs to operate with high quality DNA.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>генотипирование</kwd><kwd>микроорганизмы</kwd><kwd>молекулярно-генетические методы</kwd><kwd>genotyping</kwd><kwd>microorganisms</kwd><kwd>molecular-genetic methods</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Yang Y, Wang J, Wen H, Liu H. Comparison of two suspension arrays for simultaneous detection of five biothreat bacterial in powder samples. J Biomed Biotechnol. 2012; 2012: 831052. doi: 10.1155/2012/831052.</mixed-citation><mixed-citation xml:lang="en">Yang Y, Wang J, Wen H, Liu H. Comparison of two suspension arrays for simultaneous detection of five biothreat bacterial in powder samples. J Biomed Biotechnol. 2012; 2012: 831052. doi: 10.1155/2012/831052.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Бондарева ОС, Савченко СС, Ткаченко ГА, Абуева АИ, Муратова ЮО, Антонов ВА. Современные подходы к генотипированию возбудителей особо опасных инфекций. Эпидемиология и инфекционные болезни 2014; (1): 34-44.</mixed-citation><mixed-citation xml:lang="en">Bondareva OS, Savchenko SS, Tkachenko GA, Abueva AI, Muratova SO, Antonov VA. Modern approaches to genotyping of pathogens of especially dangerous infections. Epidemiologiya i infektsionnye bolezni 2014; (1): 34–44 (in Russian).</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Сколотнева ЕС, Волкова РА, Эльберт ЕВ, Миронов АН, Меркулов ВА, Бондарев ВП, Борисевич ИВ. Методы генотипирования бактерий: фрагментный анализ. Биопрепараты 2014; (2): 13-21.</mixed-citation><mixed-citation xml:lang="en">Skolotneva ES, Volkova RA, Elbert EV, Mironov AN, Merkulov VA, Bondarev VP, Borisevich IV. Bacterial genotyping methods: banding pattern-based analysis. Biopreparaty 2014; (2): 13–21 (in Russian).</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Волкова РА, Сколотнева ЕС, Эльберт ЕВ, Мыца ЕД, Миронов АН, Меркулов ВА, Бондарев ВП, Борисевич ИВ. Прямые и косвенные методы определения нуклеотидного состава ДНК последовательностей микроорганизмов. Биопрепараты 2015; (2): 9-16.</mixed-citation><mixed-citation xml:lang="en">Volkova RA, Skolotneva ES, Elbert EV, Mytsa ED, Merkulov VA, Bondarev VP, Borisevich IV. Direct and indirect methods of determining DNA nucleotide sequences in microorganisms. Biopreparaty 2015; (2): 9–16 (in Russian).</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Power EG. RAPD typing in microbiology - a technical review. J Hosp Infect. 1996; 34: 247-65.</mixed-citation><mixed-citation xml:lang="en">Power EG. RAPD typing in microbiology — a technical review. J Hosp Infect. 1996; 34: 247–65.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Rezk NA, Mansour H, Ghoneim NH, Rifaat MM. Typing of Salmonella typhi strains isolated from Egypt by RAPD PCR. Biothech. 2012; 2(1): 17-25.</mixed-citation><mixed-citation xml:lang="en">Rezk NA, Mansour H, Ghoneim NH, Rifaat MM. Typing of Salmonella typhi strains isolated from Egypt by RAPD PCR. Biothech. 2012; 2(1): 17–25.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Fournier PE, Zhu Y, Ogata H, Raoult D. Use of highly variable intergenetic spacer sequences for multispacer typing of Rickettsia conorii strains. J Clin Microbiol. 2004; 42: 5757-66.</mixed-citation><mixed-citation xml:lang="en">Fournier PE, Zhu Y, Ogata H, Raoult D. Use of highly variable intergenetic spacer sequences for multispacer typing of Rickettsia conorii strains. J Clin Microbiol. 2004; 42: 5757–66.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Li W, Chomel BB, Maruyama S, Guptil L, Sander A, Raoult D, et al. Multispacer typing to study the genotypic distribution of Bartonella henselae populations. J Clin Microbiol. 2006; 44: 2499-506.</mixed-citation><mixed-citation xml:lang="en">Li W, Chomel BB, Maruyama S, Guptil L, Sander A, Raoult D, et al. Multispacer typing to study the genotypic distribution of Bartonella henselae populations. J Clin Microbiol. 2006; 44: 2499–506.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">van Belkum A, Scherer S, Verbrugh H. Short-sequence DNA repeats in prokaryotic genomes. Microbiol Mol Biol R. 1998; 62: 275-93.</mixed-citation><mixed-citation xml:lang="en">van Belkum A, Scherer S, Verbrugh H. Short-sequence DNA repeats in prokaryotic genomes. Microbiol Mol Biol R. 1998; 62: 275–93.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Li W, Raoult D, Fournier P. Bacterial strain typing in the genomic era. FEMS Microbiology Rev. 2009; 33(5): 892-916.</mixed-citation><mixed-citation xml:lang="en">Li W, Raoult D, Fournier P. Bacterial strain typing in the genomic era. FEMS Microbiology Rev. 2009; 33(5): 892–916.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Cooper JE, Feil EJ. Multilocus sequence typing - what is resolved? Trends Microbiol. 2004; 12: 373-7.</mixed-citation><mixed-citation xml:lang="en">Cooper JE, Feil EJ. Multilocus sequence typing — what is resolved? Trends Microbiol. 2004; 12: 373–7.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Сухих ГТ, Павлова ГВ, Рысков АП, Бутовская ПР, Мартиросян ИА. Способ контроля за генетической изменчивостью в культуре животных клеток различной длительности пассирования. Патент Российской Федерации, № 2392330 С2; 2006.</mixed-citation><mixed-citation xml:lang="en">Suhih GT, Pavlova GV, Ryskov AP, Butovskaya PR, Martirosyan IA. The method of monitoring the genetic variability in animal cell culture passage of varying duration. Patent RF, ¹ 2392330 C2; 2006 (in Russian).</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Kellenberger E. Exploring the unknown. The silent revolution of microbiology. EMBO Rep. 2001; (2): 5-7.</mixed-citation><mixed-citation xml:lang="en">Kellenberger E. Exploring the unknown. The silent revolution of microbiology. EMBO Rep. 2001; (2): 5–7.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Rappe MS, Giovannoni SJ. The uncultured microbial majority. Annu Rev Microbiol. 2003; 57: 369-94.</mixed-citation><mixed-citation xml:lang="en">Rappe MS, Giovannoni SJ. The uncultured microbial majority. Annu Rev Microbiol. 2003; 57: 369–94.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Sabat AJ, Budimir A, Nashev D, Sá-Leão R, van Dijl JM, Laurent F, et al. Overview of molecular typing methods for outbreak detection and epidemiological surveillance. Euro Surveill. 2013; 18(4): 20380.</mixed-citation><mixed-citation xml:lang="en">Sabat AJ, Budimir A, Nashev D, Sá-Leão R, van Dijl JM, Laurent F, et al. Overview of molecular typing methods for outbreak detection and epidemiological surveillance. Euro Surveill. 2013; 18(4): 20380.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Aguiar-Alves F, Medeiros F, Fernandes O, Pereira RM, Perdreau-Remington F, Riley L. New Staphylococcus aureus genotyping method based on exotoxin (set) genes. J Clin Microbiol. 2006; 44: 2728-32.</mixed-citation><mixed-citation xml:lang="en">Aguiar-Alves F, Medeiros F, Fernandes O, Pereira RM, Perdreau-Remington F, Riley L. New Staphylococcus aureus genotyping method based on exotoxin (set) genes. J Clin Microbiol. 2006; 44: 2728–32.</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Miya S, Kimura B, Sato M, Takahashi H, Ishikawa T, Suda T, et al. Development of a multilocus variable-number of tandem repeat typing method for Listeria monocytogenes serotype 4b strains. Int J Food Microbiol. 2008; 124(3): 239-49.</mixed-citation><mixed-citation xml:lang="en">Miya S, Kimura B, Sato M, Takahashi H, Ishikawa T, Suda T, et al. Development of a multilocus variable-number of tandem repeat typing method for Listeria monocytogenes serotype 4b strains. Int J Food Microbiol. 2008; 124(3): 239–49.</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Chuang Y, Wang J, Chen M, Chen YC. Comparison of an automated repetitive-sequence-based PCR microbial typing system with pulsed-field gel electrophoresis for molecular typing of vancomycin-resistant Enterococcus faecium. J Clin Microbiol. 2010; 48: 2897-901.</mixed-citation><mixed-citation xml:lang="en">Chuang Y, Wang J, Chen M, Chen YC. Comparison of an automated repetitive-sequence-based PCR microbial typing system with pulsed-field gel electrophoresis for molecular typing of vancomycin-resistant Enterococcus faecium. J Clin Microbiol. 2010; 48: 2897–901.</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Souza RA, Falcão JP. A novel high-resolution melting analysis-based method for Yersinia pseudotuberculosis genotyping. J Microbiol Meth. 2012; 91(3): 329-35.</mixed-citation><mixed-citation xml:lang="en">Souza RA, Falcão JP. A novel high-resolution melting analysis-based method for Yersinia pseudotuberculosis genotyping. J Microbiol Meth. 2012; 91(3): 329–35.</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Knight R, Jansson J, Field D, Fierer N, Desai N, Fuhrman JA, et al. Unlocking the potential of metagenomics through replicated experimental design. Nature Biotechnology 2012; 30: 513-20.</mixed-citation><mixed-citation xml:lang="en">Knight R, Jansson J, Field D, Fierer N, Desai N, Fuhrman JA, et al. Unlocking the potential of metagenomics through replicated experimental design. Nature Biotechnology 2012; 30: 513–20.</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Antonov AV, Mewes HW. Complex phylogenetic profiling reveals fundamental genotype-phenotype associations. Comput Biol Chem. 2008; 32: 412-6.</mixed-citation><mixed-citation xml:lang="en">Antonov AV, Mewes HW. Complex phylogenetic profiling reveals fundamental genotype–phenotype associations. Comput Biol Chem. 2008; 32: 412–6.</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Benfey PN, Mitchell-Olds T. From genotype to phenotype: systems biology meets natural variation. Science. 2008; 320: 495-7.</mixed-citation><mixed-citation xml:lang="en">Benfey PN, Mitchell-Olds T. From genotype to phenotype: systems biology meets natural variation. Science. 2008; 320: 495–7.</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Harris SR, Cartwright EJP, Török ME, et al. Whole-genome sequencing for analysis of an outbreak of meticillin-resistant Staphylococcus aureus: a descriptive study. Lancet Infect Dis. 2013; 13(2): 130-6.</mixed-citation><mixed-citation xml:lang="en">Harris SR, Cartwright EJP, Török ME, et al. Whole-genome sequencing for analysis of an outbreak of meticillin-resistant Staphylococcus aureus: a descriptive study. Lancet Infect Dis. 2013; 13(2): 130–6.</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">Тотолян АА. Современные подходы и технологии в инфекционной эпидемиологии (на примере инфекций, вызываемых патогенными стрептококками). Журнал инфектологии 2012; 4(3): 88-100.</mixed-citation><mixed-citation xml:lang="en">Totolyan AA. Modern technologies and approaches in the epidemiology of infectious (for example, infections caused by pathogenic streptococci). Zhurnal infektologii 2012; 4(3): 88–100 (in Russian).</mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">Kīser CU, Ellington MJ, Cartwright EJP, Gillespie SH, Brown NM, Farrington M, et al. Routine use of microbial whole genome sequencing in diagnostic and public health microbiology. PLoS Pathogen 2012; 8(8): 1-9.</mixed-citation><mixed-citation xml:lang="en">Kîser CU, Ellington MJ, Cartwright EJP, Gillespie SH, Brown NM, Farrington M, et al. Routine use of microbial whole genome sequencing in diagnostic and public health microbiology. PLoS Pathogen 2012; 8(8): 1–9.</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru">Алексеева АЕ, Бруснигина НФ. Возможности и перспективы применения методов массивного параллельного секвенирования в диагностике и эпидемиологическом надзоре за инфекционными заболеваниями (аналитический обзор). Медиаль 2014; 2(12): 1-28.</mixed-citation><mixed-citation xml:lang="en">Alekseeva AE, Brusnigina NF. Opportunities and prospects of massive parallel sequencing methods in the diagnosis and epidemiological surveillance of communicable diseases (analytical review). Medial 2014; 2(12): 1–28 (in Russian).</mixed-citation></citation-alternatives></ref><ref id="cit27"><label>27</label><citation-alternatives><mixed-citation xml:lang="ru">Pareek CS, Smoczynski R, Tretyn A. Sequencing technologies and genome sequencing. J Appl Genetics. 2011; 52(4): 413-35.</mixed-citation><mixed-citation xml:lang="en">Pareek CS, Smoczynski R, Tretyn A. Sequencing technologies and genome sequencing. J Appl Genetics. 2011; 52(4): 413–35.</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
