Mismatch and G-Stack Modulated Probe Signals on SNP Microarrays
Publication Date
November 17, 2009
Journal
PLOS ONE
Authors
Hans Binder, Mario Fasold & Torsten Glomb
Volume
4
Issue
11
Pages
e7862
DOI
https://dx.plos.org/10.1371/journal.pone.0007862
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0007862
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/19924253
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2775684
Europe PMC
http://europepmc.org/abstract/MED/19924253
Web of Science
000271854200010
Scopus
70849095709
Mendeley
http://www.mendeley.com/research/mismatch-gstack-modulated-probe-signals-snp-microarrays
Events
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Mendeley 1525 Apr 02:16 UTC

Mendeley | Further Information

{"title"=>"Mismatch and G-stack modulated probe signals on SNP microarrays", "type"=>"journal", "authors"=>[{"first_name"=>"Hans", "last_name"=>"Binder", "scopus_author_id"=>"7202460187"}, {"first_name"=>"Mario", "last_name"=>"Fasold", "scopus_author_id"=>"35319704900"}, {"first_name"=>"Torsten", "last_name"=>"Glomb", "scopus_author_id"=>"35319582500"}], "year"=>2009, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"70849095709", "doi"=>"10.1371/journal.pone.0007862", "pui"=>"355724720", "issn"=>"19326203", "pmid"=>"19924253", "scopus"=>"2-s2.0-70849095709"}, "id"=>"f0d6f9d5-4843-38f7-a241-beb13c854db8", "abstract"=>"BACKGROUND: Single nucleotide polymorphism (SNP) arrays are important tools widely used for genotyping and copy number estimation. This technology utilizes the specific affinity of fragmented DNA for binding to surface-attached oligonucleotide DNA probes. We analyze the variability of the probe signals of Affymetrix GeneChip SNP arrays as a function of the probe sequence to identify relevant sequence motifs which potentially cause systematic biases of genotyping and copy number estimates. METHODOLOGY/PRINCIPAL FINDINGS: The probe design of GeneChip SNP arrays enables us to disentangle different sources of intensity modulations such as the number of mismatches per duplex, matched and mismatched base pairings including nearest and next-nearest neighbors and their position along the probe sequence. The effect of probe sequence was estimated in terms of triple-motifs with central matches and mismatches which include all 256 combinations of possible base pairings. The probe/target interactions on the chip can be decomposed into nearest neighbor contributions which correlate well with free energy terms of DNA/DNA-interactions in solution. The effect of mismatches is about twice as large as that of canonical pairings. Runs of guanines (G) and the particular type of mismatched pairings formed in cross-allelic probe/target duplexes constitute sources of systematic biases of the probe signals with consequences for genotyping and copy number estimates. The poly-G effect seems to be related to the crowded arrangement of probes which facilitates complex formation of neighboring probes with at minimum three adjacent G's in their sequence. CONCLUSIONS: The applied method of \"triple-averaging\" represents a model-free approach to estimate the mean intensity contributions of different sequence motifs which can be applied in calibration algorithms to correct signal values for sequence effects. Rules for appropriate sequence corrections are suggested.", "link"=>"http://www.mendeley.com/research/mismatch-gstack-modulated-probe-signals-snp-microarrays", "reader_count"=>15, "reader_count_by_academic_status"=>{"Researcher"=>5, "Student > Ph. D. Student"=>4, "Student > Postgraduate"=>1, "Student > Master"=>2, "Other"=>1, "Student > Bachelor"=>2}, "reader_count_by_user_role"=>{"Researcher"=>5, "Student > Ph. D. Student"=>4, "Student > Postgraduate"=>1, "Student > Master"=>2, "Other"=>1, "Student > Bachelor"=>2}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>3, "Medicine and Dentistry"=>1, "Agricultural and Biological Sciences"=>7, "Chemistry"=>1, "Computer Science"=>2, "Earth and Planetary Sciences"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Chemistry"=>{"Chemistry"=>1}, "Earth and Planetary Sciences"=>{"Earth and Planetary Sciences"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>7}, "Computer Science"=>{"Computer Science"=>2}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}}, "reader_count_by_country"=>{"Austria"=>1, "United States"=>1, "Germany"=>1}, "group_count"=>0}
Scopus 717 Feb 08:15 UTC

Scopus | Further Information

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Figshare08 Jan 17:32 UTC

Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/434280"], "description"=>"<div><h3>Background</h3><p>Single nucleotide polymorphism (SNP) arrays are important tools widely used for genotyping and copy number estimation. This technology utilizes the specific affinity of fragmented DNA for binding to surface-attached oligonucleotide DNA probes. We analyze the variability of the probe signals of Affymetrix GeneChip SNP arrays as a function of the probe sequence to identify relevant sequence motifs which potentially cause systematic biases of genotyping and copy number estimates.</p><h3>Methodology/Principal Findings</h3><p>The probe design of GeneChip SNP arrays enables us to disentangle different sources of intensity modulations such as the number of mismatches per duplex, matched and mismatched base pairings including nearest and next-nearest neighbors and their position along the probe sequence. The effect of probe sequence was estimated in terms of triple-motifs with central matches and mismatches which include all 256 combinations of possible base pairings. The probe/target interactions on the chip can be decomposed into nearest neighbor contributions which correlate well with free energy terms of DNA/DNA-interactions in solution. The effect of mismatches is about twice as large as that of canonical pairings. Runs of guanines (G) and the particular type of mismatched pairings formed in cross-allelic probe/target duplexes constitute sources of systematic biases of the probe signals with consequences for genotyping and copy number estimates. The poly-G effect seems to be related to the crowded arrangement of probes which facilitates complex formation of neighboring probes with at minimum three adjacent G's in their sequence.</p><h3>Conclusions</h3><p>The applied method of “triple-averaging” represents a model-free approach to estimate the mean intensity contributions of different sequence motifs which can be applied in calibration algorithms to correct signal values for sequence effects. Rules for appropriate sequence corrections are suggested.</p></div>", "links"=>[], "tags"=>["mismatch", "g-stack", "modulated", "probe", "signals", "snp", "microarrays"], "article_id"=>145685, "categories"=>["Genetics", "Biophysics", "Biotechnology", "Cancer"], "users"=>["Hans Binder", "Mario Fasold", "Torsten Glomb"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0007862"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Mismatch_and_G_Stack_Modulated_Probe_Signals_on_SNP_Microarrays/145685", "title"=>"Mismatch and G-Stack Modulated Probe Signals on SNP Microarrays", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2009-11-17 01:34:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/875454"], "description"=>"<p>(a) Each SNP (for example [C/A]) is probed by 25meric probes of complementary sequence. Different offsets δ of the SNP position relative to the middle base (mb) of the probe sequence are used. In addition, each PM probe is paired with one MM probe the middle base of which mismatches the target sequence (not shown). (b) The allele-specific probes intend to detect the respective targets via allele-specific binding which however competes with cross-allelic hybridization of targets of the alternative allele (see also the reaction equation Eq. (6)). (c) Both hybridization modes give rise to four different types of probe/target duplexes formed by the two allele-specific probes. The figure shows the respective base pairings for a selected SNP-triple which consists of the SNP [C/T] and its nearest neighbors. Mismatched non-canonical pairings are indicated by crosses. (d) Each box includes one probe-quartet which consists of two PM/MM-probe pairs interrogating either targets of allele G = A or targets of allele G' = B and vice versa (i.e. G = B and G' = A). Only targets of one allele are assumed to be present as in the sample. They hybridize to the probes of both allele sets forming either specific or cross-allelic duplexes, respectively. The three selected probe quartets differ in the offset δ of the SNP position (see arrows and part a of the figure) relatively to the middle base of the probe. The different combinations give rise to different numbers and positions of mismatched pairings which are indicated by the bulges. Their number varies between #mm = 0 and #mm = 2 in dependence on the probe type, hybridization mode and offset position. Complete probe-sets use 10 probe quartets.</p>", "links"=>[], "tags"=>["hybridization", "modes", "snp"], "article_id"=>545915, "categories"=>["Genetics", "Biophysics", "Biotechnology", "Virology"], "users"=>["Hans Binder", "Mario Fasold", "Torsten Glomb"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0007862.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Probe_design_and_hybridization_modes_for_SNP_detection_/545915", "title"=>"Probe design and hybridization modes for SNP detection.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-11-17 01:38:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/875608"], "description"=>"<p>Averaged log-intensities for probes of different mismatch-groups and offset-positions, (panel a) and mean effect of the number of mismatches (#mm) on the observed intensity (panel b). Panel a: Mean probe intensity (averaged over all probes with a given SNP offset, see the arrow in the schematic drawing in the right part for illustration) as a function of the offset-position of the mismatch with respect to the middle base (δ) for different number of mismatches per probe/target duplex (#mm = 0…2). Virtually no significant effect of the offset-position was observed for single mismatches within the relevant range |δ|<5. Contrarily, the mean intensity decreases with increasing separation between double mismatches (#mm = 2) where one is located in the centre of the probe (middle base, mb) and the second one at offset position δ. Note that both mismatches merge into one for δ = 0. The homozygous-absent data (P-G'•G) were separately calculated for the three groups of mismatches, Aa, Ac and Ag: The respective curves are almost identical. Panel b: Relative decrease of the mean probe intensity as a function of #mm (symbols). The curves are calculated using Eqs. (9) and (10). The data are shown in logarithmic (left axis, upper data) and linear (right axis) scale without (open symbols) and with (solid symbols) background correction.</p>", "links"=>[], "tags"=>["offset"], "article_id"=>546071, "categories"=>["Genetics", "Biophysics", "Biotechnology", "Virology"], "users"=>["Hans Binder", "Mario Fasold", "Torsten Glomb"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0007862.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_SNP_offset_and_number_of_mismatches_/546071", "title"=>"SNP offset and number of mismatches.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-11-17 01:41:11"}
  • {"files"=>["https://ndownloader.figshare.com/files/875809"], "description"=>"<p>Panel a: Single base data of allele-specific (S-mode) PM and MM probes. Each data point was calculated as log-intensity average over all probes of the considered class with the indicated base at position k of the probe sequence. It is associated either with WC pairings or with mismatched pairings at the middle base (mb)-position of the MM. These mismatches give rise to markedly larger variability of the intensities than the WC pairings do at the remaining positions. Panel b shows the positional dependence of the sensitivity (deviation of the log-intensity from its mean over all probes of the class) of cross-allelic PM probes (C-mode) with different offsets of the SNP. The base at the SNP position forms a mismatched pairing which shifts along the sequence according to the offset. Note that the mismatch-values are averages over all groups (Aa, Ag, Ac; see <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007862#pone.0007862.s001\" target=\"_blank\">Text S1</a>) whereas the mismatches in part a of the figure refer to the Aa-group. Panel c enlarges the single-base curves for PM-G•G shown in panel a. In addition, mean log-intensity values were calculated for homo-triples along the probe sequence (the position k refers to the center base of the triples). The mean log-intensities slightly increase for AAA, CCC and TTT compared with the single-base averages but markedly decrease for triple guanines. Panel d shows the respective single-base and triple values for the cross-allelic PM data for offset δ = 0 shown in panel b. Comparison with panel c indicates subtle differences of the curves at positions which refer to WC pairings in both situations: For example, triple-guanines motifs give rise to relatively large intensities near the surface end of the probe and also the cytosines (C- and especially CCC-motifs) are associated with largest intensities for most of the WC pairings in part d whereas thymines give rise to largest intensities in part c.</p>", "links"=>[], "tags"=>["dependence", "probe"], "article_id"=>546268, "categories"=>["Genetics", "Biophysics", "Biotechnology", "Virology"], "users"=>["Hans Binder", "Mario Fasold", "Torsten Glomb"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0007862.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Positional_dependence_of_the_probe_intensities_/546268", "title"=>"Positional dependence of the probe intensities.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-11-17 01:44:28"}
  • {"files"=>["https://ndownloader.figshare.com/files/876023"], "description"=>"<p>The triple values are calculated using (Eq. (8)) and ranked with increasing sensitivity for each center base B forming matched (group At) and different mismatched (groups Aa, Ag and Ac) pairings with the target as indicated in the figure by upper (probe) and lower (target) letters. The sensitivity-values are calculated relative to the total log-average of all single-mismatched probes of the chip. Sub-averages of the interaction groups (see arrows) and of the central base pairings are shown by vertical solid lines. The vertical dashed lines indicate the standard deviation of the triple values about the central-base related mean (see also <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007862#pone-0007862-t001\" target=\"_blank\">Table 1</a>). The mean and the standard deviation estimate the stability of the respective pairing Bb and the effect of flanking WC pairings, respectively. The error bars indicate the standard error of the triple sensitivities.</p>", "links"=>[], "tags"=>["averaged"], "article_id"=>546492, "categories"=>["Genetics", "Biophysics", "Biotechnology", "Virology"], "users"=>["Hans Binder", "Mario Fasold", "Torsten Glomb"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0007862.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Triple_averaged_sensitivities_/546492", "title"=>"Triple averaged sensitivities.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-11-17 01:48:12"}
  • {"files"=>["https://ndownloader.figshare.com/files/876258"], "description"=>"<p>The triple sensitivities, Y(xBy), of each interaction groups are ranked in decreasing order and shown by thick lines. For each base-triple three sensitivity values are shown according to Eq. (14) to reveal 3′/5′-asymmetry, Y(yBx), and complementarity, Y(y<sup>c</sup>B<sup>r</sup>x<sup>c</sup>), respectively (symbols are assigned in the figure). The abscissa labels indicate the xBy-triple. The letter-triples in the boxes indicate special triples the sensitivity values of which reveal considerable asymmetry, for example xBy/yBx/y<sup>c</sup>B<sup>r</sup>x<sup>c</sup> = TCG/GCT/AGC of the At-group. Note that GGG-motifs are highly non-complementary in all four interaction groups. Note also the markedly different widths of the scattering funnels of the different interaction groups given by their standard deviation (see dotted lines and also <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007862#pone-0007862-t001\" target=\"_blank\">Table 1</a>) indicating that the stacking terms and/or asymmetry of interactions are differently modulated by the central mismatch (see text). For symmetry reasons part of the asymmetries differences vanish (e.g. 3′/5′-asymmetry of GGG/GGG/CAC).</p>", "links"=>[], "tags"=>["relations", "triple"], "article_id"=>546716, "categories"=>["Genetics", "Biophysics", "Biotechnology", "Virology"], "users"=>["Hans Binder", "Mario Fasold", "Torsten Glomb"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0007862.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Symmetry_relations_of_triple_interactions_/546716", "title"=>"Symmetry relations of triple interactions.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-11-17 01:51:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/876396"], "description"=>"<p>Mean sensitivity values were calculated as averages over triple sensitivities shown in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007862#pone-0007862-g004\" target=\"_blank\">Figure 4</a> for each Ab-group over the central mismatch. The obtained values characterize the mean effect of the couple xy in the triple xBy. They are ranked with decreasing mean of all three mismatch groups. It shows that x,y = C and G give rise to largest sensitivities and standard deviation about the mean whereas adjacent x,y = A and T cause smaller sensitivities and variability about the mean.</p>", "links"=>[], "tags"=>["adjacent", "wc", "pairings", "triples"], "article_id"=>546860, "categories"=>["Genetics", "Biophysics", "Biotechnology", "Virology"], "users"=>["Hans Binder", "Mario Fasold", "Torsten Glomb"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0007862.g006"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_effect_of_adjacent_WC_pairings_in_triples_with_a_central_mismatch_/546860", "title"=>"The effect of adjacent WC pairings in triples with a central mismatch.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-11-17 01:54:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/876577"], "description"=>"<p>The quadruplets were analyzed in terms of independent duplets of the WC-couples xy (part a), of tandem mismatches BB' (part b) and of mixed NN-couples xB/Bx and yB'/B'y (part c and d). Note that B refers to the Aa-group whereas B' to the Aa-, Ag- or Ac-group (see legends in the figure). Along the x-axis the respective pairings are ordered with decreasing mean sensitivity which is averaged over the three groups Aa, Ag and Ac of B' (see the thick decaying curve). Part a and b: The central tandem mismatches formed by B and B' cause considerably larger scattering than the adjacent WC pairings formed by x and y. The thin dotted curves running parallel to the thick line illustrate the standard deviation of the dots about their mean (see also <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007862#pone-0007862-t001\" target=\"_blank\">Table 1</a>). In part c and d the respective NN-terms derived from the triple motifs with single mismatches (see Eq. (16) and <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007862#pone-0007862-g010\" target=\"_blank\">Figure 10</a> below) are shown for comparison (the open symbols show the NN-terms of the respective interaction groups and the thick blue line their mean value).</p>", "links"=>[], "tags"=>["sensitivities", "quadruplets", "composed", "tandem", "mismatches", "edging", "wc"], "article_id"=>547032, "categories"=>["Genetics", "Biophysics", "Biotechnology", "Virology"], "users"=>["Hans Binder", "Mario Fasold", "Torsten Glomb"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0007862.g007"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_sensitivities_of_quadruplets_xBB_y_composed_of_central_tandem_mismatches_BB_and_edging_WC_pairings_x_y_/547032", "title"=>"The sensitivities of quadruplets (xBB'y) composed of central tandem mismatches BB' and edging WC pairings, x,y.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-11-17 01:57:12"}
  • {"files"=>["https://ndownloader.figshare.com/files/876779"], "description"=>"<p>The respective probes with flanking triples are selected according to <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007862#pone.0007862.s001\" target=\"_blank\">Text S1</a>. Neglecting 3′/5′- and probe/target-asymmetries, each value is calculated as mean value over the four triples indicated at the lower and upper x-axes for each mismatch group (symbols; see legend for assignments). The combination of triples shown at the lower axis denote the complements w(xBy)m/w(x<sup>c</sup>B<sup>c</sup>y<sup>c</sup>)m and that at the upper axis m(yBx)w/m(y<sup>c</sup>B<sup>c</sup>x<sup>c</sup>)y. The thick line refers to the total mean over all three mismatch groups m∈Aa,Ag,Ac. The excess values are consistently positive and negative for adjacent y = A,T and y = C,G, respectively.</p>", "links"=>[], "tags"=>["sensitivities", "triples", "flanking", "mismatches"], "article_id"=>547239, "categories"=>["Genetics", "Biophysics", "Biotechnology", "Virology"], "users"=>["Hans Binder", "Mario Fasold", "Torsten Glomb"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0007862.g008"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Excess_sensitivities_of_triples_with_flanking_mismatches_Eq_15_/547239", "title"=>"Excess sensitivities of triples with flanking mismatches (Eq. (15)).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-11-17 02:00:39"}
  • {"files"=>["https://ndownloader.figshare.com/files/876946"], "description"=>"<p>The symbols refer to the mismatched interaction groups. The triples are ranked with decreasing residual contributions of the At-group. The horizontal dashed lines mark the average standard deviation of the data about the abscissa. The two NNN-lists indicate the largest positive (left list) and negative (right list) residual-values of the At-group. Note that triple GGG provides by far the largest (negative) residual contribution (see red circles). Positive contributions are obtained for triples containing the couple ‘GG’ which indicates that the respective NN-terms underestimate their contribution to the triple sensitivities.</p>", "links"=>[], "tags"=>["decomposition", "triple", "sensitivities", "nn-terms"], "article_id"=>547403, "categories"=>["Genetics", "Biophysics", "Biotechnology", "Virology"], "users"=>["Hans Binder", "Mario Fasold", "Torsten Glomb"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0007862.g009"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Residual_sensitivity_after_decomposition_of_the_triple_sensitivities_into_NN_terms_Eq_17_/547403", "title"=>"Residual sensitivity after decomposition of the triple sensitivities into NN-terms (Eq. (17)).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-11-17 02:03:23"}
  • {"files"=>["https://ndownloader.figshare.com/files/877150"], "description"=>"<p>The NN-terms are calculated via decomposition of the triple terms using SVD (Eq. (16)) where the base couples are ordered with respect to the centre base B of the triples. The base couples are indicated as abscissa labels x<u>B</u>/<u>B</u>x (left/right bar, respectively). The symbols are the sensitivities after applying the complementary transformation to the NN-terms, xB→B<sup>r</sup>x<sup>c</sup>. NN-terms related to ‘GG’-motifs are indicated by red circles. They strongly deviate from the complementary condition.</p>", "links"=>[], "tags"=>["biophysics/experimental biophysical methods", "biotechnology/small molecule chemistry", "computational biology/sequence motif analysis", "genetics and genomics/bioinformatics", "genetics and genomics/gene discovery"], "article_id"=>547607, "categories"=>["Genetics", "Biophysics", "Biotechnology", "Virology"], "users"=>["Hans Binder", "Mario Fasold", "Torsten Glomb"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0007862.g010"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Nearest_neighbor_NN_sensitivity_terms_of_the_four_interaction_groups_/547607", "title"=>"Nearest neighbor (NN) sensitivity terms of the four interaction groups.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-11-17 02:06:47"}
  • {"files"=>["https://ndownloader.figshare.com/files/877312"], "description"=>"<p>The figure shows the sensitivity NN-terms of the At- (part a) and Aa- (part b) groups obtained in this study (Eq. (16)) with NN-stacking free energy terms for DNA/DNA-duplexes in solution taken from ref. <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007862#pone.0007862-SantaLucia2\" target=\"_blank\">[33]</a> and <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007862#pone.0007862-Peyret1\" target=\"_blank\">[31]</a>, respectively. The dashed diagonal lines are linear regressions using all NN-data except the double-guanine terms (At-group) and in addition except TT and TG (Aa-group) which are included in red circles (regression coefficients and slopes are given in the figure). Panel a: Each NN-sensitivity of couple XY was calculated as the mean value averaged over the two sensitivities with arguments X<u>Y</u> and <u>X</u>Y shown in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007862#pone-0007862-g010\" target=\"_blank\">Figure 10</a>. The difference between these paired values is shown by the error bars which typically do not exceed the size of the symbol. The basic set of 10 independent terms is indicated by open circles. Panel b: The complementary couples x<u>B</u> and <u>B</u><sup>r</sup>x<sup>c</sup> are shown by different triangles. Only selected NN-motifs are assigned. The apparent mean stabilities of the mismatched pairings rank differently for chip (see vertical bar) and solution (horizontal bar) data.</p>", "links"=>[], "tags"=>["biophysics/experimental biophysical methods", "biotechnology/small molecule chemistry", "computational biology/sequence motif analysis", "genetics and genomics/bioinformatics", "genetics and genomics/gene discovery"], "article_id"=>547769, "categories"=>["Genetics", "Biophysics", "Biotechnology", "Virology"], "users"=>["Hans Binder", "Mario Fasold", "Torsten Glomb"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0007862.g011"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Comparison_with_solution_data_/547769", "title"=>"Comparison with solution data.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-11-17 02:09:29"}
  • {"files"=>["https://ndownloader.figshare.com/files/877489"], "description"=>"<p>Relative stabilities of the 10 possible contexts of complementary triples containing the 16 possible central base pairings (mismatches or Watson-Crick base pairs, see legend in the figure). The sensitivities of the pairs of complementary triples xBy/y<sup>c</sup>B<sup>r</sup>x<sup>c</sup> (B<sup>r</sup> = B') are averaged using the triple data shown in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007862#pone-0007862-g004\" target=\"_blank\">Figure 4</a>. The error bars indicate the difference between the individual values and thus they quantify the deviation from complementary symmetry. The form of the bar diagram was chosen in correspondence with <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007862#pone-0007862-g003\" target=\"_blank\">Figure 3</a> in ref. <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007862#pone.0007862-Peyret1\" target=\"_blank\">[31]</a> which ranks the stacking free energies of each triple in solution-duplexes with decreasing stability (from left to right for each triple). The mean log-intensity increment of one mismatched pairing (see <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007862#pone-0007862-g002\" target=\"_blank\">Figure 2</a>) was added to the triple-values of the At-group to compare the stabilities of WC- and mismatched pairings in a unique scale. The sensitivities of the four triple-combinations in the GGG-context are exceptionally small (see the red arrows).</p>", "links"=>[], "tags"=>["mismatch"], "article_id"=>547949, "categories"=>["Genetics", "Biophysics", "Biotechnology", "Virology"], "users"=>["Hans Binder", "Mario Fasold", "Torsten Glomb"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0007862.g012"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Stability_of_mismatch_motifs_/547949", "title"=>"Stability of mismatch motifs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-11-17 02:12:29"}
  • {"files"=>["https://ndownloader.figshare.com/files/877577"], "description"=>"<p>The sensitivity values are averaged over all sequence positions of homo-motifs of length 1 to 5 of homozygous present probes (PM-G'•G, see also <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007862#pone-0007862-g003\" target=\"_blank\">Figure 3</a>). Adenines, cytosines and thymines follow straight lines the slope of which is related to the mean stability increment per additional WC pairing in the runs. For guanines the absolute value of the slope drastically increases by more than one order of magnitude for longer poly-G runs exceeding two adjacent G. This effect is attributed to the formation of stacks of at minimum three G-tetrads (G4, see the sketch within the figure which illustrates the structure of a parallel quadruplex formed by four neighbored probe oligomers with GGG-runs at the same sequence position; they are assumed to aggregate into three G4-layers).</p>", "links"=>[], "tags"=>["runs"], "article_id"=>548037, "categories"=>["Genetics", "Biophysics", "Biotechnology", "Virology"], "users"=>["Hans Binder", "Mario Fasold", "Torsten Glomb"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0007862.g013"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Sensitivities_of_runs_of_identical_bases_/548037", "title"=>"Sensitivities of runs of identical bases.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-11-17 02:13:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/877683"], "description"=>"a<p>variability estimates are separately calculated as standard deviation for each Ab-interaction group: SD = √<Δ<sup>2</sup>><sub>Ab</sub>.</p>b<p>variability of the triple averages with respect to the group-mean: Δ = Y<sub>Ab</sub>(xBy)−Ab(xBy)><sub>Ab</sub>; it estimates the variability of interactions due to the choice of the triple; the standard error refers to the variability of the probe level data of each interaction group.</p>c<p>variability of the triple averages after 3′/5′-transformation: Δ = Y<sub>Ab</sub>(xBy)−Y<sub>Ab</sub>(yBx).</p>d<p>variability of the triple averages after complementary-transformation: Δ = Y<sub>Ab</sub>(xBy)−Y<sub>Ab</sub>(x<sup>c</sup>B<sup>r</sup>y<sup>c</sup>); the values in the brackets are obtained after omitting the GGG-motif.</p>e<p>variability of the residual values after reduction of the model rank NNN→NN: Δ = Δ<sup>res</sup><sub>Ab</sub> (see Eq. (17)).</p>f<p>variability due to flanking mismatches: Δ = Δ<sup>flank</sup><sub>Ab</sub> (see Eq. (15)).</p>g<p>variability due to quadruplet motifs with tandem mismatches (xBB'y)/(yB'Bx) with B∈Aa and B'∈Aa,Ag,Ac. The SD were calculated with respect to the average over the three groups (Δ(xy) = Ab(xBB'y)><sub>BB'</sub>−<Ab(xBB'y)><sub>BB'</sub>><sub>Ab</sub> and Δ(BB') = Ab(xBB'y)><sub>xy</sub>−<Ab(xBB'y)><sub>xy</sub>><sub>Ab</sub>) and with respect to the total mean over all couples (values in the brackets; (Δ(xy) = Ab(xBB'y)><sub>BB'</sub>−<Ab(xBB'y)><sub>BB'</sub>><sub>Ab,xy</sub> and Δ(BB') = Ab(xBB'y)><sub>xy</sub>−<Ab(xBB'y)><sub>xy</sub>><sub>Ab,BB'</sub>).</p>", "links"=>[], "tags"=>["variability", "triple", "motifs", "tandem"], "article_id"=>548140, "categories"=>["Genetics", "Biophysics", "Biotechnology", "Virology"], "users"=>["Hans Binder", "Mario Fasold", "Torsten Glomb"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0007862.t001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Sources_of_variability_of_triple_motifs_and_of_tandem_mismatches_/548140", "title"=>"Sources of variability of triple motifs and of tandem mismatches.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2009-11-17 02:15:40"}
PMC Usage Stats 88917 Feb 15:20 UTC

PMC Usage Stats | Further Information

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Relative Metric 64638319 Apr 16:43 UTC

Relative Metric

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