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==Introduction==
==Introduction==
The increased throughput, coupled with reduced cost and time, of contemporary sequencing technologies has led to a surge in the number of publicly available, complete, annotated genomic sequences. For smaller viral species, it is now feasible to not only produce a single genome for a species but also capture the diversity present in an ecological niche, the focus of numerous metagenomic studies<ref name="FiererMeta07">{{cite journal |title=Metagenomic and small-subunit rRNA analyses reveal the genetic diversity of bacteria, archaea, fungi, and viruses in soil |journal=Applied and Environmental Microbiology |author=Fierer, N.; Breitbart, M.; Nulton, J. et al. |volume=73 |issue=21 |pages=7059-66 |year=2007 |doi=10.1128/AEM.00358-07 |pmid=17827313 |pmc=PMC2074941}}</ref><ref name="HolmfeldtTwelve13">{{cite journal |title=Twelve previously unknown phage genera are ubiquitous in global oceans |journal=Proceedings of the National Academy of Sciences of the United States of America |author=Holmfeldt, K.; Solonenko, N.; Shah, M. et al. |volume=110 |issue=31 |pages=12798-803 |year=2013 |doi=10.1073/pnas.1305956110 |pmid=23858439 |pmc=PMC3732932}}</ref><ref name="HurwitzThePac13">{{cite journal |title=The Pacific Ocean Virome (POV): A marine viral metagenomic dataset and associated protein clusters for quantitative viral ecology |journal=PLoS One |author=Hurwitz, B.L.; Sullivan, M.B. |volume=8 |issue=2 |pages=e57355 |year=2013 |doi=10.1371/journal.pone.0057355 |pmid=23468974 |pmc=PMC3585363}}</ref> as well as more targeted investigations.<ref name="DengViral14">{{cite journal |title=Viral tagging reveals discrete populations in ''Synechococcus'' viral genome sequence space |journal=Nature |author=Deng, L.; Ignacio-Espinoza, J.C.; Gregory, A.C. |volume=513 |issue=7517 |pages=242-5 |year=2014 |doi=10.1038/nature13459 |pmid=25043051}}</ref> Furthermore, next-generation sequencing technologies have tremendous potential for the future of diagnostics and subsequent treatment choices, particularly for viral infections.<ref name="BarzonApp11">{{cite journal |title=Applications of next-generation sequencing technologies to diagnostic virology |journal=International Journal of Medical Sciences |author=Barzon, L.; Lavezzo, E.; Militello, V. et al. |volume=12 |issue=11 |pages=7861-84 |year=2011 |doi=10.3390/ijms12117861 |pmid=22174638 |pmc=PMC3233444}}</ref> The sensitivity of deep sequencing can capture even rare variants in mixed infections as well as quasispecies.<ref name="WangChar07">{{cite journal |title=Characterization of mutation spectra with ultra-deep pyrosequencing: Application to HIV-1 drug resistance |journal=Genome Research |author=Wang, C.; Mitsuya, Y.; Gharizadeh, B. et al. |volume=17 |issue=8 |pages=1195-201 |year=2007 |doi=10.1101/gr.6468307 |pmid=17600086 |pmc=PMC1933516}}</ref><ref name="RamakrishnanTheFeas09">{{cite journal |title=The feasibility of using high resolution genome sequencing of influenza A viruses to detect mixed infections and quasispecies |journal=PLoS One |author=Ramakrishnan, M.A.; Tu, Z.J.; Singh, S. et al. |volume=4 |issue=9 |pages=e7105 |year=2009 |doi=10.1371/journal.pone.0007105 |pmid=19771155 |pmc=PMC2740821}}</ref><ref name="SolmoneUse09">{{cite journal |title=Use of massively parallel ultradeep pyrosequencing to characterize the genetic diversity of hepatitis B virus in drug-resistant and drug-naive patients and to detect minor variants in reverse transcriptase and hepatitis B S antigen |journal=Journal of Virology |author=Solmone, M.; Vincenti, D.; Prosperi, M.C. et al. |volume=83 |issue=4 |pages=1718-26 |year=2009 |doi=10.1128/JVI.02011-08 |pmid=19073746 |pmc=PMC2643754}}</ref><ref name="AbdelrahmanNext15">{{cite journal |title=Next-generation sequencing sheds light on the natural history of hepatitis C infection in patients who fail treatment |journal=Hepatology |author=Abdelrahman, T.; Hughes, J.; Main, J. et al. |volume=61 |issue=1 |pages=88–97 |year=2015 |doi=10.1002/hep.27192 |pmid=24797101 |pmc=PMC4303934}}</ref><ref name="VerheyenComp06">{{cite journal |title=Compensatory mutations at the HIV cleavage sites p7/p1 and p1/p6-gag in therapy-naive and therapy-experienced patients |journal=Antiviral Therapy |author=Verheyen, J.; Litau, E.; Sing, T. et al. |volume=11 |issue=7 |pages=879-87 |year=2006 |pmid=17302250}}</ref><ref name="Quiñones-MateuDeep14">{{cite journal |title=Deep sequencing: becoming a critical tool in clinical virology |journal=Journal of Clinical Virology |author=Quiñones-Mateu, M.E.; Avila, S.; Reyes-Teran, G.; Martinez, M.A. |volume=61 |issue=1 |pages=9–19 |year=2015 |doi=10.1016/j.jcv.2014.06.013 |pmid=24998424 |pmc=PMC4119849}}</ref> Investigation of the viable variations within a viral species not only provides insight into the evolutionary history of a species but also unveils putative avenues for targeted therapies, such as small interfering RNAs<ref name="LaresRNA10">{{cite journal |title=RNAi and small interfering RNAs in human disease therapeutic applications |journal=Trends in Biotechnology |author=Lares, M.R.; Rossi, J.J.; Ouellet, D.L. |volume=28 |issue=11 |pages=570-9 |year=2010 |doi=10.1016/j.tibtech.2010.07.009 |pmid=20833440 |pmc=PMC2955826}}</ref><ref name="TruongAnInf13">{{cite journal |title=An influenza virus-inspired polymer system for the timed release of siRNA |journal=Nature Communications |author=Truong, N.P.; Gu, W.; Prasadam, I. et al. |volume=4 |pages=1902 |year=2013 |doi=10.1038/ncomms2905 |pmid=23695696}}</ref><ref name="PaulDeliv14">{{cite journal |title=Delivery of antiviral small interfering RNA with gold nanoparticles inhibits dengue virus infection in vitro |journal=Journal of General Virology |author=Paul, A.M.; Shi, Y.; Acharya, D. et al. |volume=95 |issue=Pt 8 |pages=1712-22 |year=2014 |doi=10.1099/vir.0.066084-0 |pmid=24828333 |pmc=PMC4103068}}</ref><ref name="JinSilen14">{{cite journal |title=Silencing herpes simplex virus type 1 capsid protein encoding genes by siRNA: a promising antiviral therapeutic approach |journal=PLoS One |author=Jin, F.; Li, S.; Zheng, K. et al. |volume=9 |issue=5 |pages=e96623 |year=2014 |doi=10.1371/journal.pone.0096623 |pmid=24794394 |pmc=PMC4008601}}</ref> and control strategies.
The increased throughput, coupled with reduced cost and time, of contemporary sequencing technologies has led to a surge in the number of publicly available, complete, annotated genomic sequences. For smaller viral species, it is now feasible to not only produce a single genome for a species but also capture the diversity present in an ecological niche, the focus of numerous metagenomic studies<ref name="FiererMeta07">{{cite journal |title=Metagenomic and small-subunit rRNA analyses reveal the genetic diversity of bacteria, archaea, fungi, and viruses in soil |journal=Applied and Environmental Microbiology |author=Fierer, N.; Breitbart, M.; Nulton, J. et al. |volume=73 |issue=21 |pages=7059-66 |year=2007 |doi=10.1128/AEM.00358-07 |pmid=17827313 |pmc=PMC2074941}}</ref><ref name="HolmfeldtTwelve13">{{cite journal |title=Twelve previously unknown phage genera are ubiquitous in global oceans |journal=Proceedings of the National Academy of Sciences of the United States of America |author=Holmfeldt, K.; Solonenko, N.; Shah, M. et al. |volume=110 |issue=31 |pages=12798-803 |year=2013 |doi=10.1073/pnas.1305956110 |pmid=23858439 |pmc=PMC3732932}}</ref><ref name="HurwitzThePac13">{{cite journal |title=The Pacific Ocean Virome (POV): A marine viral metagenomic dataset and associated protein clusters for quantitative viral ecology |journal=PLoS One |author=Hurwitz, B.L.; Sullivan, M.B. |volume=8 |issue=2 |pages=e57355 |year=2013 |doi=10.1371/journal.pone.0057355 |pmid=23468974 |pmc=PMC3585363}}</ref> as well as more targeted investigations.<ref name="DengViral14">{{cite journal |title=Viral tagging reveals discrete populations in ''Synechococcus'' viral genome sequence space |journal=Nature |author=Deng, L.; Ignacio-Espinoza, J.C.; Gregory, A.C. |volume=513 |issue=7517 |pages=242-5 |year=2014 |doi=10.1038/nature13459 |pmid=25043051}}</ref> Furthermore, next-generation sequencing technologies have tremendous potential for the future of diagnostics and subsequent treatment choices, particularly for viral infections.<ref name="BarzonApp11">{{cite journal |title=Applications of next-generation sequencing technologies to diagnostic virology |journal=International Journal of Medical Sciences |author=Barzon, L.; Lavezzo, E.; Militello, V. et al. |volume=12 |issue=11 |pages=7861-84 |year=2011 |doi=10.3390/ijms12117861 |pmid=22174638 |pmc=PMC3233444}}</ref> The sensitivity of deep sequencing can capture even rare variants in mixed infections as well as quasispecies.<ref name="WangChar07">{{cite journal |title=Characterization of mutation spectra with ultra-deep pyrosequencing: Application to HIV-1 drug resistance |journal=Genome Research |author=Wang, C.; Mitsuya, Y.; Gharizadeh, B. et al. |volume=17 |issue=8 |pages=1195-201 |year=2007 |doi=10.1101/gr.6468307 |pmid=17600086 |pmc=PMC1933516}}</ref><ref name="RamakrishnanTheFeas09">{{cite journal |title=The feasibility of using high resolution genome sequencing of influenza A viruses to detect mixed infections and quasispecies |journal=PLoS One |author=Ramakrishnan, M.A.; Tu, Z.J.; Singh, S. et al. |volume=4 |issue=9 |pages=e7105 |year=2009 |doi=10.1371/journal.pone.0007105 |pmid=19771155 |pmc=PMC2740821}}</ref><ref name="SolmoneUse09">{{cite journal |title=Use of massively parallel ultradeep pyrosequencing to characterize the genetic diversity of hepatitis B virus in drug-resistant and drug-naive patients and to detect minor variants in reverse transcriptase and hepatitis B S antigen |journal=Journal of Virology |author=Solmone, M.; Vincenti, D.; Prosperi, M.C. et al. |volume=83 |issue=4 |pages=1718-26 |year=2009 |doi=10.1128/JVI.02011-08 |pmid=19073746 |pmc=PMC2643754}}</ref><ref name="AbdelrahmanNext15">{{cite journal |title=Next-generation sequencing sheds light on the natural history of hepatitis C infection in patients who fail treatment |journal=Hepatology |author=Abdelrahman, T.; Hughes, J.; Main, J. et al. |volume=61 |issue=1 |pages=88–97 |year=2015 |doi=10.1002/hep.27192 |pmid=24797101 |pmc=PMC4303934}}</ref><ref name="VerheyenComp06">{{cite journal |title=Compensatory mutations at the HIV cleavage sites p7/p1 and p1/p6-gag in therapy-naive and therapy-experienced patients |journal=Antiviral Therapy |author=Verheyen, J.; Litau, E.; Sing, T. et al. |volume=11 |issue=7 |pages=879-87 |year=2006 |pmid=17302250}}</ref><ref name="Quiñones-MateuDeep14">{{cite journal |title=Deep sequencing: becoming a critical tool in clinical virology |journal=Journal of Clinical Virology |author=Quiñones-Mateu, M.E.; Avila, S.; Reyes-Teran, G.; Martinez, M.A. |volume=61 |issue=1 |pages=9–19 |year=2015 |doi=10.1016/j.jcv.2014.06.013 |pmid=24998424 |pmc=PMC4119849}}</ref> Investigation of the viable variations within a viral species not only provides insight into the evolutionary history of a species but also unveils putative avenues for targeted therapies, such as small interfering RNAs<ref name="LaresRNA10">{{cite journal |title=RNAi and small interfering RNAs in human disease therapeutic applications |journal=Trends in Biotechnology |author=Lares, M.R.; Rossi, J.J.; Ouellet, D.L. |volume=28 |issue=11 |pages=570-9 |year=2010 |doi=10.1016/j.tibtech.2010.07.009 |pmid=20833440 |pmc=PMC2955826}}</ref><ref name="TruongAnInf13">{{cite journal |title=An influenza virus-inspired polymer system for the timed release of siRNA |journal=Nature Communications |author=Truong, N.P.; Gu, W.; Prasadam, I. et al. |volume=4 |pages=1902 |year=2013 |doi=10.1038/ncomms2905 |pmid=23695696}}</ref><ref name="PaulDeliv14">{{cite journal |title=Delivery of antiviral small interfering RNA with gold nanoparticles inhibits dengue virus infection in vitro |journal=Journal of General Virology |author=Paul, A.M.; Shi, Y.; Acharya, D. et al. |volume=95 |issue=Pt 8 |pages=1712-22 |year=2014 |doi=10.1099/vir.0.066084-0 |pmid=24828333 |pmc=PMC4103068}}</ref><ref name="JinSilen14">{{cite journal |title=Silencing herpes simplex virus type 1 capsid protein encoding genes by siRNA: A promising antiviral therapeutic approach |journal=PLoS One |author=Jin, F.; Li, S.; Zheng, K. et al. |volume=9 |issue=5 |pages=e96623 |year=2014 |doi=10.1371/journal.pone.0096623 |pmid=24794394 |pmc=PMC4008601}}</ref> and control strategies.
 
Molecular biology is now plagued with the challenges facing numerous other fields – big data. Cloud-based solutions, e.g. CloudBurst<ref name="SchatzCloud09">{{cite journal |title=CloudBurst: Highly sensitive read mapping with MapReduce |journal=Bioinformatics |author=Schatz, M.C. |volume=25 |issue=11 |pages=1363-9 |year=2009 |doi=10.1093/bioinformatics/btp236 |pmid=19357099 |pmc=PMC2682523}}</ref>, Atlas2<ref name="EvaniAtlas12">{{cite journal |title=Atlas2 Cloud: A framework for personal genome analysis in the cloud |journal=BMC Genomics |author=Evani, U.S.; Challis, D.; Yu, J. et al. |volume=13 |issue=Suppl 6 |pages=S19 |year=2012 |doi=10.1186/1471-2164-13-S6-S19 |pmid=23134663 |pmc=PMC3481437}}</ref>, and Rainbow<ref name="ZhaoRainbow13">{{cite journal |title=Rainbow: A tool for large-scale whole-genome sequencing data analysis using cloud computing |journal=BMC Genomics |author=Zhao, S.; Prenger, K.; Smith, L. et al. |volume=14 |pages=425 |year=2013 |doi=10.1186/1471-2164-14-425 |pmid=23802613 |pmc=PMC3698007}}</ref>, have provided much needed leverage to meet these demands, facilitating large-scale sequence analyses, while also introducing new difficulties.<ref name="SchatzCloud10">{{cite journal |title=Cloud computing and the DNA data race |journal=Nature Biotechnology |author=Schatz, M.C.; Langmead, B.; Salzberg, S.L. |volume=28 |pages=7 |year=2010 |doi=10.1038/nbt0710-691 |pmid=20622843 |pmc=PMC2904649}}</ref> Furthermore, noSQL databases afford a streamlined solution to both manage large datasets and simplify data retrieval and subsequent analysis. The added benefit of agility and scalability of noSQL databases is ideal for the rapidly advancing trends in DNA sequencing technologies, and it is thus not surprising that noSQL databases have been gaining traction in molecular studies.<ref name="BorozanCaPSID12">{{cite journal |title=CaPSID: A bioinformatics platform for computational pathogen sequence identification in human genomes and transcriptomes |journal=BMC Bioinformatics |author=Borozan, I.; Wilson, S.; Blanchette, P. |volume=13 |pages=206 |year=2012 |doi=10.1186/1471-2105-13-206 |pmid=22901030 |pmc=PMC3464663}}</ref><ref name="Hird_lociNGS12">{{cite journal |title=lociNGS: A lightweight alternative for assessing suitability of next-generation loci for evolutionary analysis |journal=PLoS One |author=Hird, S.M. |volume=7 |issue=10 |pages=e46847 |year=2012 |doi=10.1371/journal.pone.0046847 |pmid=23071651 |pmc=PMC3468592}}</ref><ref name="NingthoujamNoSQL14">{{cite journal |title=NoSQL data model for semi-automatic integration of ethnomedicinal plant data from multiple sources |journal=Phytochemical Analysis |author=Ningthoujam, S.S.; Choudhury, M.D.; Potsangbam, K.S. et al. |volume=25 |issue=6 |pages=495-507 |year=2014 |doi=10.1002/pca.2520 |pmid=24737485}}</ref>


==References==
==References==

Revision as of 17:35, 5 May 2016

Full article title A polyglot approach to bioinformatics data integration: A phylogenetic analysis of HIV-1
Journal Evolutionary Bioinformatics
Author(s) Reisman, S.; Hatzopoulos, T.; Läufer, K.; Thiruvathukal, G.K.; Putonti, C.
Author affiliation(s) Loyola University Chicago
Primary contact Email: cputonti@luc.edu
Year published 2016
Volume and issue 12
Page(s) 23–27
DOI 10.4137/EBO.S32757
ISSN 1176-9343
Distribution license Creative Commons Attribution-NonCommercial 3.0 Unported
Website http://www.la-press.com/
Download http://www.la-press.com/ (PDF)
This article should not be considered complete until this message box has been removed. This is a work in progress.

Abstract

As sequencing technologies continue to drop in price and increase in throughput, new challenges emerge for the management and accessibility of genomic sequence data. We have developed a pipeline for facilitating the storage, retrieval, and subsequent analysis of molecular data, integrating both sequence and metadata. Taking a polyglot approach involving multiple languages, libraries, and persistence mechanisms, sequence data can be aggregated from publicly available and local repositories. Data are exposed in the form of a RESTful web service, formatted for easy querying, and retrieved for downstream analyses. As a proof of concept, we have developed a resource for annotated HIV-1 sequences. Phylogenetic analyses were conducted for >6,000 HIV-1 sequences revealing spatial and temporal factors influence the evolution of the individual genes uniquely. Nevertheless, signatures of origin can be extrapolated even despite increased globalization. The approach developed here can easily be customized for any species of interest.

Keywords: polyglot programming, RESTful web service, phylogenetics

Introduction

The increased throughput, coupled with reduced cost and time, of contemporary sequencing technologies has led to a surge in the number of publicly available, complete, annotated genomic sequences. For smaller viral species, it is now feasible to not only produce a single genome for a species but also capture the diversity present in an ecological niche, the focus of numerous metagenomic studies[1][2][3] as well as more targeted investigations.[4] Furthermore, next-generation sequencing technologies have tremendous potential for the future of diagnostics and subsequent treatment choices, particularly for viral infections.[5] The sensitivity of deep sequencing can capture even rare variants in mixed infections as well as quasispecies.[6][7][8][9][10][11] Investigation of the viable variations within a viral species not only provides insight into the evolutionary history of a species but also unveils putative avenues for targeted therapies, such as small interfering RNAs[12][13][14][15] and control strategies.

Molecular biology is now plagued with the challenges facing numerous other fields – big data. Cloud-based solutions, e.g. CloudBurst[16], Atlas2[17], and Rainbow[18], have provided much needed leverage to meet these demands, facilitating large-scale sequence analyses, while also introducing new difficulties.[19] Furthermore, noSQL databases afford a streamlined solution to both manage large datasets and simplify data retrieval and subsequent analysis. The added benefit of agility and scalability of noSQL databases is ideal for the rapidly advancing trends in DNA sequencing technologies, and it is thus not surprising that noSQL databases have been gaining traction in molecular studies.[20][21][22]

References

  1. ↑ Fierer, N.; Breitbart, M.; Nulton, J. et al. (2007). "Metagenomic and small-subunit rRNA analyses reveal the genetic diversity of bacteria, archaea, fungi, and viruses in soil". Applied and Environmental Microbiology 73 (21): 7059-66. doi:10.1128/AEM.00358-07. PMC PMC2074941. PMID 17827313. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2074941. 
  2. ↑ Holmfeldt, K.; Solonenko, N.; Shah, M. et al. (2013). "Twelve previously unknown phage genera are ubiquitous in global oceans". Proceedings of the National Academy of Sciences of the United States of America 110 (31): 12798-803. doi:10.1073/pnas.1305956110. PMC PMC3732932. PMID 23858439. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3732932. 
  3. ↑ Hurwitz, B.L.; Sullivan, M.B. (2013). "The Pacific Ocean Virome (POV): A marine viral metagenomic dataset and associated protein clusters for quantitative viral ecology". PLoS One 8 (2): e57355. doi:10.1371/journal.pone.0057355. PMC PMC3585363. PMID 23468974. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3585363. 
  4. ↑ Deng, L.; Ignacio-Espinoza, J.C.; Gregory, A.C. (2014). "Viral tagging reveals discrete populations in Synechococcus viral genome sequence space". Nature 513 (7517): 242-5. doi:10.1038/nature13459. PMID 25043051. 
  5. ↑ Barzon, L.; Lavezzo, E.; Militello, V. et al. (2011). "Applications of next-generation sequencing technologies to diagnostic virology". International Journal of Medical Sciences 12 (11): 7861-84. doi:10.3390/ijms12117861. PMC PMC3233444. PMID 22174638. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3233444. 
  6. ↑ Wang, C.; Mitsuya, Y.; Gharizadeh, B. et al. (2007). "Characterization of mutation spectra with ultra-deep pyrosequencing: Application to HIV-1 drug resistance". Genome Research 17 (8): 1195-201. doi:10.1101/gr.6468307. PMC PMC1933516. PMID 17600086. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1933516. 
  7. ↑ Ramakrishnan, M.A.; Tu, Z.J.; Singh, S. et al. (2009). "The feasibility of using high resolution genome sequencing of influenza A viruses to detect mixed infections and quasispecies". PLoS One 4 (9): e7105. doi:10.1371/journal.pone.0007105. PMC PMC2740821. PMID 19771155. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2740821. 
  8. ↑ Solmone, M.; Vincenti, D.; Prosperi, M.C. et al. (2009). "Use of massively parallel ultradeep pyrosequencing to characterize the genetic diversity of hepatitis B virus in drug-resistant and drug-naive patients and to detect minor variants in reverse transcriptase and hepatitis B S antigen". Journal of Virology 83 (4): 1718-26. doi:10.1128/JVI.02011-08. PMC PMC2643754. PMID 19073746. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2643754. 
  9. ↑ Abdelrahman, T.; Hughes, J.; Main, J. et al. (2015). "Next-generation sequencing sheds light on the natural history of hepatitis C infection in patients who fail treatment". Hepatology 61 (1): 88–97. doi:10.1002/hep.27192. PMC PMC4303934. PMID 24797101. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4303934. 
  10. ↑ Verheyen, J.; Litau, E.; Sing, T. et al. (2006). "Compensatory mutations at the HIV cleavage sites p7/p1 and p1/p6-gag in therapy-naive and therapy-experienced patients". Antiviral Therapy 11 (7): 879-87. PMID 17302250. 
  11. ↑ Quiñones-Mateu, M.E.; Avila, S.; Reyes-Teran, G.; Martinez, M.A. (2015). "Deep sequencing: becoming a critical tool in clinical virology". Journal of Clinical Virology 61 (1): 9–19. doi:10.1016/j.jcv.2014.06.013. PMC PMC4119849. PMID 24998424. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4119849. 
  12. ↑ Lares, M.R.; Rossi, J.J.; Ouellet, D.L. (2010). "RNAi and small interfering RNAs in human disease therapeutic applications". Trends in Biotechnology 28 (11): 570-9. doi:10.1016/j.tibtech.2010.07.009. PMC PMC2955826. PMID 20833440. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2955826. 
  13. ↑ Truong, N.P.; Gu, W.; Prasadam, I. et al. (2013). "An influenza virus-inspired polymer system for the timed release of siRNA". Nature Communications 4: 1902. doi:10.1038/ncomms2905. PMID 23695696. 
  14. ↑ Paul, A.M.; Shi, Y.; Acharya, D. et al. (2014). "Delivery of antiviral small interfering RNA with gold nanoparticles inhibits dengue virus infection in vitro". Journal of General Virology 95 (Pt 8): 1712-22. doi:10.1099/vir.0.066084-0. PMC PMC4103068. PMID 24828333. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4103068. 
  15. ↑ Jin, F.; Li, S.; Zheng, K. et al. (2014). "Silencing herpes simplex virus type 1 capsid protein encoding genes by siRNA: A promising antiviral therapeutic approach". PLoS One 9 (5): e96623. doi:10.1371/journal.pone.0096623. PMC PMC4008601. PMID 24794394. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4008601. 
  16. ↑ Schatz, M.C. (2009). "CloudBurst: Highly sensitive read mapping with MapReduce". Bioinformatics 25 (11): 1363-9. doi:10.1093/bioinformatics/btp236. PMC PMC2682523. PMID 19357099. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2682523. 
  17. ↑ Evani, U.S.; Challis, D.; Yu, J. et al. (2012). "Atlas2 Cloud: A framework for personal genome analysis in the cloud". BMC Genomics 13 (Suppl 6): S19. doi:10.1186/1471-2164-13-S6-S19. PMC PMC3481437. PMID 23134663. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3481437. 
  18. ↑ Zhao, S.; Prenger, K.; Smith, L. et al. (2013). "Rainbow: A tool for large-scale whole-genome sequencing data analysis using cloud computing". BMC Genomics 14: 425. doi:10.1186/1471-2164-14-425. PMC PMC3698007. PMID 23802613. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3698007. 
  19. ↑ Schatz, M.C.; Langmead, B.; Salzberg, S.L. (2010). "Cloud computing and the DNA data race". Nature Biotechnology 28: 7. doi:10.1038/nbt0710-691. PMC PMC2904649. PMID 20622843. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2904649. 
  20. ↑ Borozan, I.; Wilson, S.; Blanchette, P. (2012). "CaPSID: A bioinformatics platform for computational pathogen sequence identification in human genomes and transcriptomes". BMC Bioinformatics 13: 206. doi:10.1186/1471-2105-13-206. PMC PMC3464663. PMID 22901030. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3464663. 
  21. ↑ Hird, S.M. (2012). "lociNGS: A lightweight alternative for assessing suitability of next-generation loci for evolutionary analysis". PLoS One 7 (10): e46847. doi:10.1371/journal.pone.0046847. PMC PMC3468592. PMID 23071651. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3468592. 
  22. ↑ Ningthoujam, S.S.; Choudhury, M.D.; Potsangbam, K.S. et al. (2014). "NoSQL data model for semi-automatic integration of ethnomedicinal plant data from multiple sources". Phytochemical Analysis 25 (6): 495-507. doi:10.1002/pca.2520. PMID 24737485. 

Notes

This presentation is faithful to the original, with only a few minor changes to presentation. In some cases important information was missing from the references, and that information was added.

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