Modeling Formamide Denaturation of Probe-Target Hybrids for Improved Microarray Probe Design in Microbial Diagnostics
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{"title"=>"Modeling formamide denaturation of probe-target hybrids for improved microarray probe design in microbial diagnostics", "type"=>"journal", "authors"=>[{"first_name"=>"L. Safak", "last_name"=>"Yilmaz", "scopus_author_id"=>"56331992900"}, {"first_name"=>"Alexander", "last_name"=>"Loy", "scopus_author_id"=>"56243274300"}, {"first_name"=>"Erik S.", "last_name"=>"Wright", "scopus_author_id"=>"54919896700"}, {"first_name"=>"Michael", "last_name"=>"Wagner", "scopus_author_id"=>"57200814774"}, {"first_name"=>"Daniel R.", "last_name"=>"Noguera", "scopus_author_id"=>"7004620564"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"365513905", "sgr"=>"84865426331", "pmid"=>"22952791", "scopus"=>"2-s2.0-84865426331", "isbn"=>"1932-6203", "doi"=>"10.1371/journal.pone.0043862", "issn"=>"19326203"}, "id"=>"06135593-d112-3150-b823-f7b8efb17102", "abstract"=>"Application of high-density microarrays to the diagnostic analysis of microbial communities is challenged by the optimization of oligonucleotide probe sensitivity and specificity, as it is generally unfeasible to experimentally test thousands of probes. This study investigated the adjustment of hybridization stringency using formamide with the idea that sensitivity and specificity can be optimized during probe design if the hybridization efficiency of oligonucleotides with target and non-target molecules can be predicted as a function of formamide concentration. Sigmoidal denaturation profiles were obtained using fluorescently labeled and fragmented 16S rRNA gene amplicon of Escherichia coli as the target with increasing concentrations of formamide in the hybridization buffer. A linear free energy model (LFEM) was developed and microarray-specific nearest neighbor rules were derived. The model simulated formamide melting with a denaturant m-value that increased hybridization free energy (ΔG°) by 0.173 kcal/mol per percent of formamide added (v/v). Using the LFEM and specific probe sets, free energy rules were systematically established to predict the stability of single and double mismatches, including bulged and tandem mismatches. The absolute error in predicting the position of experimental denaturation profiles was less than 5% formamide for more than 90 percent of probes, enabling a practical level of accuracy in probe design. The potential of the modeling approach for probe design and optimization is demonstrated using a dataset including the 16S rRNA gene of Rhodobacter sphaeroides as an additional target molecule. The LFEM and thermodynamic databases were incorporated into a computational tool (ProbeMelt) that is freely available at http://DECIPHER.cee.wisc.edu.", "link"=>"http://www.mendeley.com/research/modeling-formamide-denaturation-probetarget-hybrids-improved-microarray-probe-design-microbial-diagn", "reader_count"=>31, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Researcher"=>7, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>13, "Student > Postgraduate"=>2, "Student > Master"=>3, "Other"=>2, "Student > Bachelor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Researcher"=>7, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>13, "Student > Postgraduate"=>2, "Student > Master"=>3, "Other"=>2, "Student > Bachelor"=>2}, "reader_count_by_subject_area"=>{"Engineering"=>1, "Unspecified"=>1, "Environmental Science"=>1, "Biochemistry, Genetics and Molecular Biology"=>2, "Agricultural and Biological Sciences"=>21, "Philosophy"=>1, "Veterinary Science and Veterinary Medicine"=>1, "Chemistry"=>3}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Chemistry"=>{"Chemistry"=>3}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>21}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Unspecified"=>{"Unspecified"=>1}, "Environmental Science"=>{"Environmental Science"=>1}, "Philosophy"=>{"Philosophy"=>1}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>1}}, "reader_count_by_country"=>{"United States"=>2}, "group_count"=>1}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/585991"], "description"=>"<p>(<b>A</b>) Perfect match (Length set), (<b>B</b>) central mismatch (OneM set; open bars, right axis) and bulged mismatch (Gap and Insertion sets; grey bars, left axis), (<b>C</b>) positional mismatch (PosM set), and (<b>D</b>) two-mismatch (TwoM set; open bars, right axis) and tandem-mismatch (Tandem set; grey bar, left axis) probes. Lower case letters indicate bins to which probes in corresponding panels of <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0043862#pone-0043862-g002\" target=\"_blank\">Figure 2</a> belong.</p>", "links"=>[], "tags"=>["microbiology", "biotechnology", "Computational biology", "biophysics", "Biochemistry"], "article_id"=>256475, "categories"=>["Biochemistry", "Biotechnology", "Biological Sciences", "Microbiology", "Biophysics"], "users"=>["L. Safak Yilmaz", "Alexander Loy", "Erik S. Wright", "Michael Wagner", "Daniel R. Noguera"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0043862.g003", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Histograms_of_prediction_errors_/256475", "title"=>"Histograms of prediction errors.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-08-27 01:47:55"}
  • {"files"=>["https://ndownloader.figshare.com/files/586389"], "description"=>"<p>The example probe, E751–772, is a perfect match to the 16S rRNA gene of <i>E. coli</i> and has one mismatch to <i>R. sphaeroides</i>. Curves are theoretical predictions fitted to the experimental scale. Eco, <i>E. coli</i>; Rsp, <i>R. sphaeroides</i>.</p>", "links"=>[], "tags"=>["denaturation", "profiles", "abundant"], "article_id"=>256874, "categories"=>["Biochemistry", "Biotechnology", "Biological Sciences", "Microbiology", "Biophysics"], "users"=>["L. Safak Yilmaz", "Alexander Loy", "Erik S. Wright", "Michael Wagner", "Daniel R. Noguera"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0043862.g007", "stats"=>{"downloads"=>4, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Formamide_denaturation_profiles_with_conventional_target_and_highly_abundant_non_target_/256874", "title"=>"Formamide denaturation profiles with conventional target and highly abundant non-target.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-08-27 01:54:34"}
  • {"files"=>["https://ndownloader.figshare.com/files/586517"], "description"=>"a<p>See <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0043862#pone-0043862-t002\" target=\"_blank\">Table 2</a> for the definition of models and parameters and the reference values. See <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0043862#pone.0043862.s007\" target=\"_blank\">Text S1</a> for the details of the statistical tests.</p>b<p>Randomization and permutation tests are based on at least 100 runs until convergence. Significant figures in these results reflect the uncertainty in the converged values.</p>c<p>Probes were permuted while maintaining the original sequence of each probe. This test corresponds to permuting the probe length in addition to the nearest neighbor free energies.</p>d<p>Show improvement over original models although statistical parameters indicate otherwise. The discrepancy reflects the fact that half-denaturation point is not a perfect representation of the melting point for experimental profiles without a plateau (e.g., see <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0043862#pone.0043862.s003\" target=\"_blank\">Figure S3C</a>). This adversely affects the results with <i>γ</i>-factors more than without, as the models without <i>γ</i>-factors tend to compensate for the lack of good fitting in the vertical by moving closer to experimental values in the horizontal, although this movement does not mean a better match. Since the original models in the main text always use <i>γ</i>-factors, the evaluation of model predictions are conservative and more accurate with respect to half-denaturation points. This analysis provides just another way of seeing how <i>γ</i>-factors buffer experimental artifacts as discussed in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0043862#pone.0043862.s007\" target=\"_blank\">Text S1</a>.</p>e<p>Best-fitted <i>γ</i> replaced by a model-derived factor (see <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0043862#pone.0043862.s007\" target=\"_blank\">Text S1</a>).</p>", "links"=>[], "tags"=>["microbiology", "biotechnology", "Computational biology", "biophysics", "Biochemistry"], "article_id"=>257000, "categories"=>["Biochemistry", "Biotechnology", "Biological Sciences", "Microbiology", "Biophysics"], "users"=>["L. Safak Yilmaz", "Alexander Loy", "Erik S. Wright", "Michael Wagner", "Daniel R. Noguera"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0043862.t003", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Additional_statistical_tests_a_b_/257000", "title"=>"Additional statistical tests<sup>a,b</sup>.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-08-27 01:56:40"}
  • {"files"=>["https://ndownloader.figshare.com/files/308949", "https://ndownloader.figshare.com/files/309202", "https://ndownloader.figshare.com/files/309289", "https://ndownloader.figshare.com/files/309368", "https://ndownloader.figshare.com/files/309448", "https://ndownloader.figshare.com/files/309474", "https://ndownloader.figshare.com/files/309537", "https://ndownloader.figshare.com/files/309656"], "description"=>"<div><p>Application of high-density microarrays to the diagnostic analysis of microbial communities is challenged by the optimization of oligonucleotide probe sensitivity and specificity, as it is generally unfeasible to experimentally test thousands of probes. This study investigated the adjustment of hybridization stringency using formamide with the idea that sensitivity and specificity can be optimized during probe design if the hybridization efficiency of oligonucleotides with target and non-target molecules can be predicted as a function of formamide concentration. Sigmoidal denaturation profiles were obtained using fluorescently labeled and fragmented 16S rRNA gene amplicon of <em>Escherichia coli</em> as the target with increasing concentrations of formamide in the hybridization buffer. A linear free energy model (LFEM) was developed and microarray-specific nearest neighbor rules were derived. The model simulated formamide melting with a denaturant <em>m</em>-value that increased hybridization free energy (ΔG°) by 0.173 kcal/mol per percent of formamide added (v/v). Using the LFEM and specific probe sets, free energy rules were systematically established to predict the stability of single and double mismatches, including bulged and tandem mismatches. The absolute error in predicting the position of experimental denaturation profiles was less than 5% formamide for more than 90 percent of probes, enabling a practical level of accuracy in probe design. The potential of the modeling approach for probe design and optimization is demonstrated using a dataset including the 16S rRNA gene of <em>Rhodobacter sphaeroides</em> as an additional target molecule. The LFEM and thermodynamic databases were incorporated into a computational tool (ProbeMelt) that is freely available at <a href=\"http://DECIPHER.cee.wisc.edu\">http://DECIPHER.cee.wisc.edu</a>.</p> </div>", "links"=>[], "tags"=>["modeling", "formamide", "denaturation", "probe-target", "hybrids", "microarray", "probe", "microbial", "diagnostics"], "article_id"=>120966, "categories"=>["Biochemistry", "Biotechnology", "Biological Sciences", "Microbiology", "Biophysics"], "users"=>["L. Safak Yilmaz", "Alexander Loy", "Erik S. Wright", "Michael Wagner", "Daniel R. Noguera"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0043862.s001", "https://dx.doi.org/10.1371/journal.pone.0043862.s002", "https://dx.doi.org/10.1371/journal.pone.0043862.s003", "https://dx.doi.org/10.1371/journal.pone.0043862.s004", "https://dx.doi.org/10.1371/journal.pone.0043862.s005", "https://dx.doi.org/10.1371/journal.pone.0043862.s006", "https://dx.doi.org/10.1371/journal.pone.0043862.s007", "https://dx.doi.org/10.1371/journal.pone.0043862.s008"], "stats"=>{"downloads"=>37, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Modeling_Formamide_Denaturation_of_Probe_Target_Hybrids_for_Improved_Microarray_Probe_Design_in_Microbial_Diagnostics/120966", "title"=>"Modeling Formamide Denaturation of Probe-Target Hybrids for Improved Microarray Probe Design in Microbial Diagnostics", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2012-08-27 00:16:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/585676"], "description"=>"<p>(<b>A</b>) Example formamide curves with perfect match, one-mismatch, and two-mismatch probes targeting the same site on 16S rRNA gene of <i>E. coli</i>. Curves represent theoretical profiles. Observed maximum signal intensity (I<sub>max</sub>), experimental ([FA]<sub>1/2,exp</sub>) and predicted ([FA]<sub>1/2,pred</sub>) half-denaturation points, and the prediction error (err[FA]<sub>1/2</sub>) are illustrated. [FA]<sub>1/2,exp</sub> is estimated by linear interpolation between two subsequent experimental points that are greater than and less than I<sub>max/2</sub>, respectively. Panels (<b>B</b>) and (<b>C</b>) show the correlation of solution-based free energy predictions with I<sub>max</sub> and [FA]<sub>1/2,exp</sub>, respectively, with r defining the Pearson’s correlation coefficient. (<b>D</b>) I<sub>max</sub> plotted against position of target site, as represented by the middle point. All data were obtained from probes belonging to the TileE set (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0043862#pone-0043862-t001\" target=\"_blank\">Table 1</a>). Amount of hybridized target was 5 ng.</p>", "links"=>[], "tags"=>["formamide", "denaturation"], "article_id"=>256163, "categories"=>["Biochemistry", "Biotechnology", "Biological Sciences", "Microbiology", "Biophysics"], "users"=>["L. Safak Yilmaz", "Alexander Loy", "Erik S. Wright", "Michael Wagner", "Daniel R. Noguera"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0043862.g001", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Characteristics_of_formamide_denaturation_profiles_/256163", "title"=>"Characteristics of formamide denaturation profiles.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-08-27 01:42:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/586169"], "description"=>"<p>(<b>A</b>) Example probe (E844–865_4GT) with lower free energy at relaxed conformation as compared to imposed duplex with one mismatch. (<b>B</b>) Experimentally observed shift in the half-denaturation point (Δ[FA]<sub>1/2,exp</sub> – open squares and black error bars) and calculated minimum free energy change (ΔΔG° - grey circles and error bars) upon insertion of a single mismatch, as a function of mismatch position. Values, averages; error bars, standard deviations.</p>", "links"=>[], "tags"=>["mismatch", "formamide"], "article_id"=>256657, "categories"=>["Biochemistry", "Biotechnology", "Biological Sciences", "Microbiology", "Biophysics"], "users"=>["L. Safak Yilmaz", "Alexander Loy", "Erik S. Wright", "Michael Wagner", "Daniel R. Noguera"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0043862.g005", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_mismatch_position_on_free_energy_and_formamide_denaturation_/256657", "title"=>"Effect of mismatch position on free energy and formamide denaturation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-08-27 01:50:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/586607"], "description"=>"a<p>Number of probes in set. Not all probes are directly used in model development (see next footnote, text, and <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0043862#pone-0043862-t002\" target=\"_blank\">Table 2</a>).</p>b<p>Probes targeting positions before the 50<sup>th</sup> and after the 1450<sup>th</sup> nucleotide (in <i>E. coli</i> positioning) were excluded from all analyses to avoid unamplified terminals of the targeted genes and other possible end effects.</p>c<p>209 probes shared with TileE set.</p>d<p>186 probes shared with OneM set.</p>e<p>Ten replicates of the probe 5′-AGAGAGAGAGAGAGAGAGAGAG-3′.</p>", "links"=>[], "tags"=>["sets"], "article_id"=>257103, "categories"=>["Biochemistry", "Biotechnology", "Biological Sciences", "Microbiology", "Biophysics"], "users"=>["L. Safak Yilmaz", "Alexander Loy", "Erik S. Wright", "Michael Wagner", "Daniel R. Noguera"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0043862.t001", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Probe_sets_used_in_modeling_/257103", "title"=>"Probe sets used in modeling.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-08-27 01:58:23"}
  • {"files"=>["https://ndownloader.figshare.com/files/586571"], "description"=>"a<p>Concluding (optimal) models are indicated in bold and their details are presented in other tables and figures.</p>b<p>SM, single (non-bulge) mismatch; BM, bulge mismatch; TM, tandem mismatch; sln, for in solution hybridization; ma, for microarray hybridization.</p>c<p>Parameters in italics are used in best-fitting. The use of additional parameters <i>α</i> and <i>β</i>, when applicable, is shown in the free energy column under model description (see text for best-fitting values). Other parameters derived using M3, M5, and M9 are the free energy rules in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0043862#pone.0043862.s005\" target=\"_blank\">Tables S1A, S1B</a>, and S1D, with 10, 104, and 8 additions, respectively.</p>d<p>N<sub>F</sub>, number of probes used in fitting; N<sub>T</sub>, total number of probes; <i>ε</i><sup>2</sup><sub>val</sub> and <i>ε</i><sup>2</sup><sub>ov</sub>, average squares of prediction errors in validation set (i.e., not used in fitting) and overall set, respectively. See Materials and Methods for other parameters.</p>e<p>Absolute value of the deviation of predicted half-denaturation point (% formamide) from the apparent experimental value, as described by its average/standard deviation (<i>µ/σ</i>) and percentage of values below 5% formamide.</p>f<p>ΔG° for perfect matches and ΔΔG° for mismatches (see Materials and Methods).</p>", "links"=>[], "tags"=>["microbiology", "biotechnology", "Computational biology", "biophysics", "Biochemistry"], "article_id"=>257053, "categories"=>["Biochemistry", "Biotechnology", "Biological Sciences", "Microbiology", "Biophysics"], "users"=>["L. Safak Yilmaz", "Alexander Loy", "Erik S. Wright", "Michael Wagner", "Daniel R. Noguera"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0043862.t002", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Model_development_and_curve_fitting_a_/257053", "title"=>"Model development and curve-fitting<sup>a</sup>.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-08-27 01:57:33"}
  • {"files"=>["https://ndownloader.figshare.com/files/585784"], "description"=>"<p>All perfect matches are from the TileE set, since only this set has mismatched versions (for examples from the Length set, see <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0043862#pone.0043862.s001\" target=\"_blank\">Figure S1A</a>). Solid and dashed curves indicate theoretical profiles for perfect matches and mismatches, respectively. x-axis, formamide concentration; y-axis, normalized signal intensity; error bars, standard deviations.</p>", "links"=>[], "tags"=>["melting", "profiles", "12", "arbitrarily", "probes", "mismatched"], "article_id"=>256270, "categories"=>["Biochemistry", "Biotechnology", "Biological Sciences", "Microbiology", "Biophysics"], "users"=>["L. Safak Yilmaz", "Alexander Loy", "Erik S. Wright", "Michael Wagner", "Daniel R. Noguera"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0043862.g002", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Formamide_melting_profiles_of_12_arbitrarily_selected_perfect_match_probes_and_their_mismatched_versions_/256270", "title"=>"Formamide melting profiles of 12 arbitrarily selected perfect match probes and their mismatched versions.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-08-27 01:44:30"}
  • {"files"=>["https://ndownloader.figshare.com/files/586114"], "description"=>"<p>Red circles, nearest neighbors; blue triangles, single mismatch loops; blue squares, single bulged mismatch loops; green dots, tandem mismatch loops.</p>", "links"=>[], "tags"=>["in-solution", "microarray"], "article_id"=>256604, "categories"=>["Biochemistry", "Biotechnology", "Biological Sciences", "Microbiology", "Biophysics"], "users"=>["L. Safak Yilmaz", "Alexander Loy", "Erik S. Wright", "Michael Wagner", "Daniel R. Noguera"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0043862.g004", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Relationship_between_in_solution_and_microarray_free_energy_values_at_42_176_C_/256604", "title"=>"Relationship between in-solution and microarray free energy values (at 42°C).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-08-27 01:50:04"}
  • {"files"=>["https://ndownloader.figshare.com/files/586285"], "description"=>"<p>Probes E338–359 (<b>A</b> and <b>C</b>) and E763–780 (<b>B</b> and <b>D</b>) are shown. Both probes perfectly match the 16S rRNA gene of both <i>E. coli</i> (Eco) and <i>R. sphaeroides</i> (Rsp).</p>", "links"=>[], "tags"=>["formamide", "denaturation"], "article_id"=>256778, "categories"=>["Biochemistry", "Biotechnology", "Biological Sciences", "Microbiology", "Biophysics"], "users"=>["L. Safak Yilmaz", "Alexander Loy", "Erik S. Wright", "Michael Wagner", "Daniel R. Noguera"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0043862.g006", "stats"=>{"downloads"=>1, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_target_concentration_and_type_of_target_molecule_on_formamide_denaturation_profiles_/256778", "title"=>"Effect of target concentration and type of target molecule on formamide denaturation profiles.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-08-27 01:52:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/586450"], "description"=>"<p>(<b>A</b>) Probes designed to have a melting point of 18–22% formamide and hybridized at 0% (red), 15% (green), and 20% (blue) formamide. Left panel, <i>E. coli</i> probes hybridized with 5 ng <i>E. coli</i> target (PM data) and 50 ng <i>R. sphaeroides</i> non-target (MM data); right panel, <i>R. sphaeroides</i> probes hybridized with 50 ng <i>R. sphaeroides</i> target (PM) and 5 ng <i>E. coli</i> non-target (MM). (<b>B</b>) The predictive power of hybridization efficiency for <i>E. coli</i> probes hybridized with 50 ng <i>R. sphaeroides</i> (dashed lines) and <i>R. sphareoides</i> probes hybridized with 5 ng <i>E.coli</i> (solid lines) for all mismatches (red), 1–2 mismatches (green), and 3–5 mismatches (blue). Data from formamide concentrations 10, 15, 20, and 25% were combined to maximize the sample space for each data point. x-axis shows midpoints of bins with a hybridization efficiency window of 0.1, except for end bins (window of 0.05).</p>", "links"=>[], "tags"=>["probes", "arbitrarily", "defined", "1750", "fluorescence"], "article_id"=>256934, "categories"=>["Biochemistry", "Biotechnology", "Biological Sciences", "Microbiology", "Biophysics"], "users"=>["L. Safak Yilmaz", "Alexander Loy", "Erik S. Wright", "Michael Wagner", "Daniel R. Noguera"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0043862.g008", "stats"=>{"downloads"=>1, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Fraction_of_probes_above_an_arbitrarily_defined_threshold_of_1750_fluorescence_units_/256934", "title"=>"Fraction of probes above an arbitrarily defined threshold of 1750 fluorescence units.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-08-27 01:55:34"}

PMC Usage Stats | Further Information

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Relative Metric

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