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{"title"=>"Transat-A method for detecting the conserved helices of functional rna structures, including transient, pseudo-knotted and alternative structures", "type"=>"journal", "authors"=>[{"first_name"=>"Nicholas J.P.", "last_name"=>"Wiebe", "scopus_author_id"=>"24473899000"}, {"first_name"=>"Irmtraud M.", "last_name"=>"Meyer", "scopus_author_id"=>"20735018600"}], "year"=>2010, "source"=>"PLoS Computational Biology", "identifiers"=>{"scopus"=>"2-s2.0-77955475692", "doi"=>"10.1371/journal.pcbi.1000823", "sgr"=>"77955475692", "isbn"=>"1553-7358 (Electronic)\\r1553-734X (Linking)", "pmid"=>"20589081", "issn"=>"1553734X", "pui"=>"359337544"}, "id"=>"40bf4f49-1a21-314c-be36-d15375ddfe5e", "abstract"=>"The prediction of functional RNA structures has attracted increased interest, as it allows us to study the potential functional roles of many genes. RNA structure prediction methods, however, assume that there is a unique functional RNA structure and also do not predict functional features required for in vivo folding. In order to understand how functional RNA structures form in vivo, we require sophisticated experiments or reliable prediction methods. So far, there exist only a few, experimentally validated transient RNA structures. On the computational side, there exist several computer programs which aim to predict the co-transcriptional folding pathway in vivo, but these make a range of simplifying assumptions and do not capture all features known to influence RNA folding in vivo. We want to investigate if evolutionarily related RNA genes fold in a similar way in vivo. To this end, we have developed a new computational method, Transat, which detects conserved helices of high statistical significance. We introduce the method, present a comprehensive performance evaluation and show that Transat is able to predict the structural features of known reference structures including pseudo-knotted ones as well as those of known alternative structural configurations. Transat can also identify unstructured sub-sequences bound by other molecules and provides evidence for new helices which may define folding pathways, supporting the notion that homologous RNA sequence not only assume a similar reference RNA structure, but also fold similarly. Finally, we show that the structural features predicted by Transat differ from those assuming thermodynamic equilibrium. Unlike the existing methods for predicting folding pathways, our method works in a comparative way. This has the disadvantage of not being able to predict features as function of time, but has the considerable advantage of highlighting conserved features and of not requiring a detailed knowledge of the cellular environment.", "link"=>"http://www.mendeley.com/research/transata-method-detecting-conserved-helices-functional-rna-structures-including-transient-pseudoknot", "reader_count"=>30, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>2, "Researcher"=>12, "Student > Ph. D. Student"=>12, "Student > Master"=>1, "Student > Bachelor"=>2, "Professor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>2, "Researcher"=>12, "Student > Ph. D. Student"=>12, "Student > Master"=>1, "Student > Bachelor"=>2, "Professor"=>1}, "reader_count_by_subject_area"=>{"Engineering"=>1, "Biochemistry, Genetics and Molecular Biology"=>6, "Agricultural and Biological Sciences"=>18, "Social Sciences"=>1, "Computer Science"=>3, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Social Sciences"=>{"Social Sciences"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>18}, "Computer Science"=>{"Computer Science"=>3}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>6}}, "reader_count_by_country"=>{"Canada"=>1, "United States"=>3, "Brazil"=>1, "Poland"=>1, "Australia"=>1, "India"=>1}, "group_count"=>0}

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• http://doi.org/10.1093/nar/gkw795
• http://doi.org/10.3389/fpls.2018.00625
• http://doi.org/10.1093/nar/gku292
• http://doi.org/10.1039/C8CP03018A
• http://doi.org/10.1093/nar/gkt319
• http://doi.org/10.1016/j.ymeth.2017.04.009
• http://doi.org/10.3390/genes9060302
• http://doi.org/10.1002/9780471729259.mc15h03s30
• http://doi.org/10.1016/j.virusres.2018.11.008
• http://doi.org/10.1016/j.sbi.2016.01.007
• http://doi.org/10.1093/nar/gks241
• http://doi.org/10.1093/bfgp/ely042
• http://doi.org/10.1371/journal.pone.0153881
• http://doi.org/10.1016/j.jsb.2019.06.005
• http://doi.org/10.1109/TCBB.2011.50
• http://doi.org/10.1186/1471-2105-15-147
• http://doi.org/10.1080/15476286.2015.1107703
• http://doi.org/10.1186/1748-7188-6-24
• http://doi.org/10.4161/rna.18488

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• {"id"=>"228167415438127105", "text"=>"@ppgardne http://t.co/9N8o8tfh", "created_at"=>"2012-07-25T16:38:45Z", "user"=>"ppgardne", "user_name"=>"Paul Gardner", "user_profile_image"=>"http://a0.twimg.com/profile_images/1247414148/seed-a-14_normal.png"}

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• {"files"=>["https://ndownloader.figshare.com/files/842496"], "description"=>"<p>See the text for more details.</p>", "links"=>[], "tags"=>["conserved", "helix"], "article_id"=>512961, "categories"=>["Medicine", "Evolutionary Biology", "Computational Biology", "Infectious Diseases", "Biophysics"], "users"=>["Nicholas J. P. Wiebe", "Irmtraud M. Meyer"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1000823.g002", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Log_likelihood_calculation_for_a_conserved_helix_detected_by_T_ransat_/512961", "title"=>"Log-likelihood calculation for a conserved helix detected by Transat.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-06-24 00:49:21"}
• {"files"=>["https://ndownloader.figshare.com/files/842437"], "description"=>"<p>Transat first predicts the helices for all individual sequences in the fixed input alignment and then maps all of them to the alignment remembering the base-pairing sequence positions. In the example above, there are two helices, one derives from sequence 1 (see top figure), the other one from sequence 2. Mapping these two helices from their respective sequence to the entire alignment results in the two potential conserved helices shown above (see the arcs linking the respective alignment columns). Both conserved helices are then evaluated by Transat in terms of log-likelihood value and p-value estimation. The log-likelihood value is calculated based on the base-paired alignment columns in that helix and all sequences in the alignment, see the text and <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1000823#pcbi-1000823-g002\" target=\"_blank\">Figure 2</a> for details. All helices predicted by Transat for a given input alignment can then be ranked according to their p-value. For the two helices in the example above, the helix that fits the sequences in the given alignment better will have the higher log-likelihood value and lower p-value. As Transat is not capable of modifying the fixed input alignment, this mapping strategy minimized the impact of alignment errors.</p>", "links"=>[], "tags"=>["helices"], "article_id"=>512899, "categories"=>["Medicine", "Evolutionary Biology", "Computational Biology", "Infectious Diseases", "Biophysics"], "users"=>["Nicholas J. P. Wiebe", "Irmtraud M. Meyer"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1000823.g001", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_T_ransat_Mapping_of_helices_to_the_alignment_/512899", "title"=>"Transat: Mapping of helices to the alignment.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-06-24 00:48:19"}
• {"files"=>["https://ndownloader.figshare.com/files/844295"], "description"=>"<p>In order to quantify the performance of Transat, base-pairs are first classified into true positives (TP), true negatives (TN), false positives (FP) and false negatives (FN) according to the definitions above, where denotes the user-defined p-value threshold which is applied to the helices predicted by Transat. The minimum p-value of a predicted base-pair is defined as the minimum p-value of all predicted helices that contain this base-pair, i.e. a predicted base-pair inherits its statistical significance from the most statistically significant helix to which it belongs.</p>", "links"=>[], "tags"=>["base-pair-specific"], "article_id"=>514756, "categories"=>["Medicine", "Evolutionary Biology", "Computational Biology", "Infectious Diseases", "Biophysics"], "users"=>["Nicholas J. P. Wiebe", "Irmtraud M. Meyer"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1000823.t001", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Definitions_regarding_the_base_pair_specific_performance_of_T_ransat_/514756", "title"=>"Definitions regarding the base-pair-specific performance of Transat.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2010-06-24 01:19:16"}
• {"files"=>["https://ndownloader.figshare.com/files/843209"], "description"=>"<p>The x-axis represents the <i>hok</i> alignment. Each arc corresponds to a base-pair between the respective positions in the alignment. Arcs above the x-axis correspond to known base-pairs, whereas arcs below correspond to new base-pairs predicted by Transat, i.e. they correspond to base-pairs that do not involve the same pair of nucleotide positions as any base-pair in the known structure(s). Base-pairs predicted by Transat have non-black colours which indicate their reliability as estimated by Transat ( green, blue, orange and (p-value threshold) red). They can either be found above the x-axis, if they agree with a pair in the reference structure(s), or below, if they are new. Transat predicts most helices of the known structure as well as three statistically significant conserved helices which may guide the structure formation.</p>", "links"=>[], "tags"=>["helices", "p-value"], "article_id"=>513670, "categories"=>["Medicine", "Evolutionary Biology", "Computational Biology", "Infectious Diseases", "Biophysics"], "users"=>["Nicholas J. P. Wiebe", "Irmtraud M. Meyer"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1000823.g009", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Conserved_helices_predicted_by_T_ransat_for_the_hok_data_set_for_different_p_value_threshold_values_left_right_/513670", "title"=>"Conserved helices predicted by Transat for the <i>hok</i> data set for different p-value threshold values (left , right ).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-06-24 01:01:10"}
• {"files"=>["https://ndownloader.figshare.com/files/843344"], "description"=>"<p>Transat predicts the helices of the pseudo-knotted known structure correctly and also predicts several transient helices which suggest a co-transcriptional folding pathway (see numbering of helices above). All predicted transient helices (helices 4, 6 and 10) are mutually incompatible with a helix of the known RNA structure. Helix 4 may yield to helix 8, helix 6 to helix 7 and helix 10 to helix 12. The transient helices may thereby guide the formation of the known functional RNA structure.</p>", "links"=>[], "tags"=>["rna", "predictions", "cripavirus", "ribosomal", "p-value"], "article_id"=>513800, "categories"=>["Medicine", "Evolutionary Biology", "Computational Biology", "Infectious Diseases", "Biophysics"], "users"=>["Nicholas J. P. Wiebe", "Irmtraud M. Meyer"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1000823.g011", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Known_RNA_secondary_structure_and_T_ransat_predictions_for_the_Cripavirus_internal_ribosomal_entry_site_IRES_RF00458_for_a_p_value_threshold_of_/513800", "title"=>"Known RNA secondary structure and Transat predictions for the Cripavirus internal ribosomal entry site (IRES), RF00458, for a p-value threshold of .", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-06-24 01:03:20"}
• {"files"=>["https://ndownloader.figshare.com/files/843141"], "description"=>"<p>The top left figures shows the sensitivity as function of the false positive rate (FPR) and the top right figure the sensitivity as function of the positive predictive value (PPV). The bottom left figure shows the F-measure and the bottom right figure the MCC as function of the p-value threshold, see the text for the definitions of the F-measure and the MCC.</p>", "links"=>[], "tags"=>["detecting", "helices"], "article_id"=>513609, "categories"=>["Medicine", "Evolutionary Biology", "Computational Biology", "Infectious Diseases", "Biophysics"], "users"=>["Nicholas J. P. Wiebe", "Irmtraud M. Meyer"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1000823.g008", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Performance_of_T_ransat_for_detecting_the_known_helices_of_the_trp_attenuator_data_set_/513609", "title"=>"Performance of Transat for detecting the known helices of the <i>trp</i>-attenuator data set.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-06-24 01:00:09"}
• {"files"=>["https://ndownloader.figshare.com/files/843276"], "description"=>"<p>The x-axis represents the <i>trp</i>-attenuator alignment, see the text or the caption of <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1000823#pcbi-1000823-g009\" target=\"_blank\">Figure 9</a> for more information on arc-plots. Transat predicts almost all base-pairs of the known structure correctly as well as several equally significant conserved helices which may guide the formation of the known structure.</p>", "links"=>[], "tags"=>["helices", "p-value"], "article_id"=>513743, "categories"=>["Medicine", "Evolutionary Biology", "Computational Biology", "Infectious Diseases", "Biophysics"], "users"=>["Nicholas J. P. Wiebe", "Irmtraud M. Meyer"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1000823.g010", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Conserved_helices_predicted_by_T_ransat_for_the_trp_attenuator_data_set_as_function_for_a_p_value_threshold_of_/513743", "title"=>"Conserved helices predicted by Transat for the <i>trp</i>-attenuator data set as function for a p-value threshold of .", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-06-24 01:02:23"}
• {"files"=>["https://ndownloader.figshare.com/files/843496"], "description"=>"<p>The Transat predictions for both RNA families indicate several, mutually incompatible transient helices. In case of the bacterial signal recognition particle, the transient helices (right, bottom, numbered 1–5) are mutually incompatible with the base-pairs of the known structure. The hairpin-like structure of the small nucleolar RNA snR76 seems to fold in one go, whereas the formation of the hairpin-like structure of the bacterial signal recognition particle RNA may first involve the formation of helix 1 which is later replaced by the known hairpin-like structure as the RNA sequence gets further transcribed. Helices 2 to 5 are predicted as statistically more significant (p-values ) than the helices of the known hairpin-like structure. They are mutually exclusive and may correspond to alternative structural confirmations for this sequence. See the text or the caption of <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1000823#pcbi-1000823-g009\" target=\"_blank\">Figure 9</a> for more information on arc-plots.</p>", "links"=>[], "tags"=>["rna", "predictions", "hairpin-like", "nucleolar", "snr76", "p-value", "bacterial"], "article_id"=>513941, "categories"=>["Medicine", "Evolutionary Biology", "Computational Biology", "Infectious Diseases", "Biophysics"], "users"=>["Nicholas J. P. Wiebe", "Irmtraud M. Meyer"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1000823.g013", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Known_RNA_secondary_structure_and_T_ransat_predictions_for_two_hairpin_like_known_structures_the_small_nucleolar_RNA_snR76_for_a_p_value_threshold_of_left_RF01209_and_the_bacterial_signal_recognition_particle_RNA_right_RF00169_for_a_p_value_threshold_of_/513941", "title"=>"Known RNA secondary structure and Transat predictions for two hairpin-like known structures, the small nucleolar RNA snR76 for a p-value threshold of (left, RF01209) and the bacterial signal recognition particle RNA (right, RF00169) for a p-value threshold of (right, top) and (right, bottom).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-06-24 01:05:41"}
• {"files"=>["https://ndownloader.figshare.com/files/842652"], "description"=>"<p>The top left figure shows the sensitivity as function of the false positive rate (FPR) and the top right figure the sensitivity (Sens) as function of the positive predictive value (PPV). The bottom left figure shows the F-measure and the bottom right figure the MCC as function of the p-value threshold, see the text for the definitions of the F-measure and the MCC. Note that each data point in the figures above corresponds to the respective performance measure averaged over the entire Rfam data set for a particular p-value threshold (along the x-axis).</p>", "links"=>[], "tags"=>["detecting", "base-pairs", "helices"], "article_id"=>513110, "categories"=>["Medicine", "Evolutionary Biology", "Computational Biology", "Infectious Diseases", "Biophysics"], "users"=>["Nicholas J. P. Wiebe", "Irmtraud M. Meyer"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1000823.g004", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Performance_of_T_ransat_for_detecting_the_known_base_pairs_bp_and_helices_helix_of_the_R_fam_data_set_/513110", "title"=>"Performance of Transat for detecting the known base-pairs (bp) and helices (helix) of the Rfam data set.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-06-24 00:51:50"}
• {"files"=>["https://ndownloader.figshare.com/files/842788"], "description"=>"<p>The top left figures shows the sensitivity (Sens) as function of the false positive rate (FPR) for different alignment lengths. The colors indicate the length of the alignment in nucleotides ranging from 100 to 999 nucleotides. The top right figures shows the sensitivity as function of the positive predictive value (PPV) for different alignment lengths. The bottom left figures shows the F-measure and the bottom right figure the MCC as function of the p-value threshold, see the text for the definitions of the F-measure and the MCC. All figures use the same coloring scheme as the top left figure.</p>", "links"=>[], "tags"=>["predicting", "helices", "alignment"], "article_id"=>513246, "categories"=>["Medicine", "Evolutionary Biology", "Computational Biology", "Infectious Diseases", "Biophysics"], "users"=>["Nicholas J. P. Wiebe", "Irmtraud M. Meyer"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1000823.g005", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Performance_of_T_ransat_for_predicting_the_known_helices_of_the_artificial_data_set_as_function_of_the_alignment_length_/513246", "title"=>"Performance of Transat for predicting the known helices of the artificial data set as function of the alignment length.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-06-24 00:54:06"}
• {"files"=>["https://ndownloader.figshare.com/files/843032"], "description"=>"<p>The top left figures shows the sensitivity as function of the false positive rate (FPR) and the top right figure the sensitivity as function of the positive predictive value (PPV). The bottom left figure shows the F-measure and the bottom right figure the MCC as function of the p-value threshold, see the text for the definitions of the F-measure and the MCC.</p>", "links"=>[], "tags"=>["detecting", "helices"], "article_id"=>513505, "categories"=>["Medicine", "Evolutionary Biology", "Computational Biology", "Infectious Diseases", "Biophysics"], "users"=>["Nicholas J. P. Wiebe", "Irmtraud M. Meyer"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1000823.g007", "stats"=>{"downloads"=>1, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Performance_of_T_ransat_for_detecting_the_known_helices_of_the_hok_data_set_/513505", "title"=>"Performance of Transat for detecting the known helices of the <i>hok</i> data set.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-06-24 00:58:25"}
• {"files"=>["https://ndownloader.figshare.com/files/843575"], "description"=>"<p>For a p-value threshold of , Transat predicts the helices of the known structures correctly and also provides strong statistical evidence (p-value ) for additional helices that would render the known secondary structure pseudo-knotted, see the blue bottom-arcs for all four RNA families. Note that for the U12 minor spliceosomal RNA (right, bottom), the newly predicted helix is in competition with the most 5′ helix that is part of the known RNA secondary structure. See the text or the caption of <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1000823#pcbi-1000823-g009\" target=\"_blank\">Figure 9</a> for more information on arc-plots.</p>", "links"=>[], "tags"=>["predictions", "pseudo-knotted", "s-adenosyl-l-homocysteine", "ribo-switch", "glms", "glucosamine-6-phosphate", "activated", "ribozyme", "nucleolar", "rna", "u3", "u12", "spliceosomal"], "article_id"=>514020, "categories"=>["Medicine", "Evolutionary Biology", "Computational Biology", "Infectious Diseases", "Biophysics"], "users"=>["Nicholas J. P. Wiebe", "Irmtraud M. Meyer"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1000823.g014", "stats"=>{"downloads"=>0, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_For_several_R_fam_families_the_T_ransat_predictions_propose_a_pseudo_knotted_configuration_see_the_S_adenosyl_L_homocysteine_ribo_switch_left_top_RF01057_the_glmS_glucosamine_6_phosphate_activated_ribozyme_left_bottom_RF00234_the_small_nucleolar_RNA_U3_r/514020", "title"=>"For several Rfam families, the Transat predictions propose a pseudo-knotted configuration, see the S-adenosyl-L-homocysteine ribo-switch (left, top, RF01057), the glmS glucosamine-6-phosphate activated ribozyme (left, bottom, RF00234), the small nucleolar RNA U3 (right, top, RF00012) and the U12 minor spliceosomal RNA (right, bottom, RF00007).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-06-24 01:07:00"}
• {"files"=>["https://ndownloader.figshare.com/files/843407"], "description"=>"<p>The Transat predictions indicate that the co-transcriptional folding of the vertebrate sequences may involve large-range structural rearrangements, whereas the two hair-pins of the known ciliate structure are predicted to form independently. Note that Transat correctly captures the known pseudo-knotted structure of the vertebrate telomerase RNA (left). See the text or the caption of <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1000823#pcbi-1000823-g009\" target=\"_blank\">Figure 9</a> for more information on arc-plots.</p>", "links"=>[], "tags"=>["rna", "predictions", "telomerase", "vertebrates", "ciliates", "p-value"], "article_id"=>513862, "categories"=>["Medicine", "Evolutionary Biology", "Computational Biology", "Infectious Diseases", "Biophysics"], "users"=>["Nicholas J. P. Wiebe", "Irmtraud M. Meyer"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1000823.g012", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Known_RNA_secondary_structure_and_T_ransat_predictions_for_telomerase_RNA_for_vertebrates_left_RF00024_and_ciliates_right_RF00025_for_a_p_value_threshold_of_/513862", "title"=>"Known RNA secondary structure and Transat predictions for telomerase RNA for vertebrates (left, RF00024) and ciliates (right, RF00025) for a p-value threshold of .", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-06-24 01:04:22"}
• {"files"=>["https://ndownloader.figshare.com/files/843826"], "description"=>"<p>In each figure, the x-axis represents the <i>hok</i> alignment. Each arc corresponds to a base-pair between the respective positions in the alignment. Arcs above the x-axis correspond to known base-pairs, whereas arcs below correspond to new base-pairs predicted by the respective program, i.e. they correspond to base-pairs that do not involve the same pair of nucleotide positions as any base-pair in the known structure(s). In the top figure, base-pairs predicted by Transat have non-black colours which indicate their reliability as estimated by Transat ( green, blue, orange) using a p-value threshold of . These base pairs can either be found above the x-axis, if they agree with a pair in the reference structure(s), or below, if they are new. In the bottom figure, base-pairs predicted by RNAalifold P have non-black colours which indicate their base-pairing probability in the Boltzmann ensemble of pseudo-knot free RNA secondary structures that we would expect in thermodynamic equilibrium ( green, blue, orange and red) using a pairing probability threshold of 5%. These base-pairs can either be found above the x-axis, if they agree with a pair in the reference structure(s), or below, if they are new. Transat predicts most helices of the known structures as well as three statistically significant conserved helices which may guide the structure formation, whereas RNAalifold P predicts only part of the known structures and contributes only a few novel base-pairs which extend a known helix by one or two base-pairs on either side, see also <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1000823#pcbi-1000823-g009\" target=\"_blank\">Figure 9</a>.</p>", "links"=>[], "tags"=>["biophysics/rna structure", "computational biology/comparative sequence analysis", "computational biology/evolutionary modeling", "computational biology/macromolecular structure analysis", "computational biology/molecular dynamics", "evolutionary biology/bioinformatics", "evolutionary biology/nuclear structure and function"], "article_id"=>514278, "categories"=>["Medicine", "Evolutionary Biology", "Computational Biology", "Infectious Diseases", "Biophysics"], "users"=>["Nicholas J. P. Wiebe", "Irmtraud M. Meyer"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1000823.g016", "stats"=>{"downloads"=>1, "page_views"=>23, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Comparison_of_T_ransat_top_figure_and_RNA_alifold_P_bottom_figure_for_the_hok_data_set_/514278", "title"=>"Comparison of Transat (top figure) and RNAalifold P (bottom figure) for the <i>hok</i> data set.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-06-24 01:11:18"}
• {"files"=>["https://ndownloader.figshare.com/files/844013"], "description"=>"<p>Transat predicts the helices of the pseudo-knotted known structure correctly and also predicts several new helices, whereas RNAalifold P captures only part of the known structure and predicts three new base-pairs which extend three known helices, see also <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1000823#pcbi-1000823-g010\" target=\"_blank\">Figure 10</a>. Please refer to the caption of <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1000823#pcbi-1000823-g016\" target=\"_blank\">Figure 16</a> for more information on these arc-plots.</p>", "links"=>[], "tags"=>["cripavirus", "ribosomal"], "article_id"=>514471, "categories"=>["Medicine", "Evolutionary Biology", "Computational Biology", "Infectious Diseases", "Biophysics"], "users"=>["Nicholas J. P. Wiebe", "Irmtraud M. Meyer"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1000823.g018", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Comparison_of_T_ransat_top_figure_and_RNA_alifold_P_bottom_figure_for_the_Cripavirus_internal_ribosomal_entry_site_IRES_RF00458_/514471", "title"=>"Comparison of Transat (top figure) and RNAalifold P (bottom figure) for the Cripavirus internal ribosomal entry site (IRES), RF00458.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-06-24 01:14:31"}
• {"files"=>["https://ndownloader.figshare.com/files/844068"], "description"=>"<p>Transat predicts the helices of the known structures correctly and also provides strong statistical evidence (p-value ) for additional helices that would render the known secondary structure pseudo-knotted, see the blue bottom-arcs. RNAalifold P predicts only part of the known structure correctly, but proposes a similar new helix, see also <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1000823#pcbi-1000823-g014\" target=\"_blank\">Figure 14</a>. Please refer to the caption of <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1000823#pcbi-1000823-g016\" target=\"_blank\">Figure 16</a> for more information on arc-plots.</p>", "links"=>[], "tags"=>["s-adenosyl-l-homocysteine"], "article_id"=>514537, "categories"=>["Medicine", "Evolutionary Biology", "Computational Biology", "Infectious Diseases", "Biophysics"], "users"=>["Nicholas J. P. Wiebe", "Irmtraud M. Meyer"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1000823.g019", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Comparison_of_T_ransat_top_figure_and_RNA_alifold_P_bottom_figure_for_the_S_adenosyl_L_homocysteine_ribo_switch_RF01057_/514537", "title"=>"Comparison of Transat (top figure) and RNAalifold P (bottom figure) for the S-adenosyl-L-homocysteine ribo-switch, RF01057.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-06-24 01:15:37"}
• {"files"=>["https://ndownloader.figshare.com/files/844331"], "description"=>"<p>In order to quantify the performance of Transat for entire helices, helices are first classified into true positives (TP), true negatives (TN), false positives (FP) and false negatives (FN) according to the definitions above, where denotes the user-defined p-value threshold which is applied to the helices predicted by Transat.</p>", "links"=>[], "tags"=>["helix-specific"], "article_id"=>514796, "categories"=>["Medicine", "Evolutionary Biology", "Computational Biology", "Infectious Diseases", "Biophysics"], "users"=>["Nicholas J. P. Wiebe", "Irmtraud M. Meyer"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1000823.t002", "stats"=>{"downloads"=>5, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Definitions_regarding_the_helix_specific_performance_of_T_ransat_/514796", "title"=>"Definitions regarding the helix-specific performance of Transat.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2010-06-24 01:19:56"}
• {"files"=>["https://ndownloader.figshare.com/files/842568"], "description"=>"<p>Transat takes as input a multiple sequence alignment and an evolutionary tree (left figure, top). It first predicts helices for all individual sequences in the alignment and then projects them back onto the multiple sequence alignment. It then calculates the log-likelihood value for each helix and estimates a p-value. The p-value estimation is explained in the right figure. In the first step, the original Transat input alignment is realigned based on primary sequence conservation only. In the second step, the columns of the resulting alignment are permuted multiple times, resulting in 500 shuffled versions of the original alignment. For each shuffled alignment, conserved helices are detected and their log-likelihood values calculated as for the original alignment. In the final step, the log-likelihood values of all helices in the shuffled alignments are entered into a histogram which is then used to derive p-values for the helices of the original alignment.</p>", "links"=>[], "tags"=>["employed"], "article_id"=>513032, "categories"=>["Medicine", "Evolutionary Biology", "Computational Biology", "Infectious Diseases", "Biophysics"], "users"=>["Nicholas J. P. Wiebe", "Irmtraud M. Meyer"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1000823.g003", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Overview_of_strategy_employed_by_T_ransat_/513032", "title"=>"Overview of strategy employed by Transat.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-06-24 00:50:32"}
• {"files"=>["https://ndownloader.figshare.com/files/842930"], "description"=>"<p>The top left figures shows the sensitivity (Sens) as function of the false positive rate (FPR) for different tree lengths. The colors indicate the total length of the maximum-likelihood trees that were derived for the alignments of the artificial data set. They range from 0.5 to 16. The top right figures shows the sensitivity as function of the positive predictive value (PPV). The bottom left figures shows the F-measure and the bottom right figure the MCC as function of the p-value threshold, see the text for the definitions of the F-measure and the MCC. All figures use the same coloring scheme as the top left figure.</p>", "links"=>[], "tags"=>["predicting", "helices"], "article_id"=>513394, "categories"=>["Medicine", "Evolutionary Biology", "Computational Biology", "Infectious Diseases", "Biophysics"], "users"=>["Nicholas J. P. Wiebe", "Irmtraud M. Meyer"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1000823.g006", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Performance_of_T_ransat_for_predicting_the_known_helices_of_the_artificial_data_set_for_different_total_tree_lengths_/513394", "title"=>"Performance of Transat for predicting the known helices of the artificial data set for different total tree lengths.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-06-24 00:56:34"}
• {"files"=>["https://ndownloader.figshare.com/files/843903"], "description"=>"<p>In the top figure showing the Transat predictions, base-pairs predicted by Transat have non-black colours which indicate their reliability as estimated by Transat ( green, blue, orange and red) using a p-value threshold of . The bottom figure shows the RNAalifold P predictions, see the caption of <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1000823#pcbi-1000823-g016\" target=\"_blank\">Figure 16</a> for more information on arc-plots. Transat predicts all helices of the known structures and several new helices, albeit with relatively high p-values between and ), whereas RNAalifold P captures only two of the helices and proposes an single new base-pair which extends of the known helices, see also <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1000823#pcbi-1000823-g010\" target=\"_blank\">Figure 10</a>.</p>", "links"=>[], "tags"=>["biophysics/rna structure", "computational biology/comparative sequence analysis", "computational biology/evolutionary modeling", "computational biology/macromolecular structure analysis", "computational biology/molecular dynamics", "evolutionary biology/bioinformatics", "evolutionary biology/nuclear structure and function"], "article_id"=>514355, "categories"=>["Medicine", "Evolutionary Biology", "Computational Biology", "Infectious Diseases", "Biophysics"], "users"=>["Nicholas J. P. Wiebe", "Irmtraud M. Meyer"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1000823.g017", "stats"=>{"downloads"=>1, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Comparison_of_T_ransat_top_figure_and_RNA_alifold_P_bottom_figure_for_the_trp_attenuator_data_set_/514355", "title"=>"Comparison of Transat (top figure) and RNAalifold P (bottom figure) for the <i>trp</i>-attenuator data set.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-06-24 01:12:35"}
• {"files"=>["https://ndownloader.figshare.com/files/843716"], "description"=>"<p>Shown here are two examples, the CsrB/RsmB RNA family (left, RF00018) and the bacterial tmRNA (right, RF00023) for a p-value threshold value of (left and right, top) and (right, bottom). The CsrB/RsmB RNA is known to be bound by multiple copies of the CsrA protein. The RNA's known structure comprises only short range helices and Transat predicts only two transient structures for the entire 392 bp long alignment. Both findings support the hypothesis that protein binding occurs early during the folding of this RNA. The helices of the pseudo-knotted known structure for the bacterial tmRNA are correctly predicted by Transat for a p-value threshold of (right, top). Transat predicts several additional helices, but the region of the tmRNA sequences that contains the reading frame which ends in a translation stop signal is devoid of statistically significant transient helices (right, bottom) supporting the hypothesis that the sequence in that region of the has been chosen to remain single-stranded and readily accessible. See the text or the caption of <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1000823#pcbi-1000823-g009\" target=\"_blank\">Figure 9</a> for more information on arc-plots.</p>", "links"=>[], "tags"=>["highlights", "regions", "devoid", "transient", "rna", "bound", "molecules", "folding"], "article_id"=>514168, "categories"=>["Medicine", "Evolutionary Biology", "Computational Biology", "Infectious Diseases", "Biophysics"], "users"=>["Nicholas J. P. Wiebe", "Irmtraud M. Meyer"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1000823.g015", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_For_some_R_fam_families_T_ransat_highlights_regions_which_are_devoid_of_transient_structures_thereby_indicating_regions_of_the_RNA_sequence_which_may_be_bound_by_other_molecules_early_on_in_the_folding_process_/514168", "title"=>"For some Rfam families, Transat highlights regions which are devoid of transient structures, thereby indicating regions of the RNA sequence which may be bound by other molecules early on in the folding process.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-06-24 01:09:28"}
• {"files"=>["https://ndownloader.figshare.com/files/419866"], "description"=>"<div><p>The prediction of functional RNA structures has attracted increased interest, as it allows us to study the potential functional roles of many genes. RNA structure prediction methods, however, assume that there is a unique functional RNA structure and also do not predict functional features required for <em>in vivo</em> folding. In order to understand how functional RNA structures form <em>in vivo</em>, we require sophisticated experiments or reliable prediction methods. So far, there exist only a few, experimentally validated transient RNA structures. On the computational side, there exist several computer programs which aim to predict the co-transcriptional folding pathway <em>in vivo</em>, but these make a range of simplifying assumptions and do not capture all features known to influence RNA folding <em>in vivo</em>. We want to investigate if evolutionarily related RNA genes fold in a similar way <em>in vivo</em>. To this end, we have developed a new computational method, Transat, which detects conserved helices of high statistical significance. We introduce the method, present a comprehensive performance evaluation and show that Transat is able to predict the structural features of known reference structures including pseudo-knotted ones as well as those of known alternative structural configurations. Transat can also identify unstructured sub-sequences bound by other molecules and provides evidence for new helices which may define folding pathways, supporting the notion that homologous RNA sequence not only assume a similar reference RNA structure, but also fold similarly. Finally, we show that the structural features predicted by Transat differ from those assuming thermodynamic equilibrium. Unlike the existing methods for predicting folding pathways, our method works in a comparative way. This has the disadvantage of not being able to predict features as function of time, but has the considerable advantage of highlighting conserved features and of not requiring a detailed knowledge of the cellular environment.</p></div>", "links"=>[], "tags"=>["detecting", "conserved", "helices", "rna", "pseudo-knotted", "structures"], "article_id"=>142906, "categories"=>["Medicine", "Evolutionary Biology", "Biological Sciences", "Cancer", "Biophysics"], "users"=>["Nicholas J. P. Wiebe", "Irmtraud M. Meyer"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1000823", "stats"=>{"downloads"=>3, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Transat_A_Method_for_Detecting_the_Conserved_Helices_of_Functional_RNA_Structures_Including_Transient_Pseudo_Knotted_and_Alternative_Structures/142906", "title"=>"Transat—A Method for Detecting the Conserved Helices of Functional RNA Structures, Including Transient, Pseudo-Knotted and Alternative Structures", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2010-06-24 00:48:26"}
• {"files"=>["https://ndownloader.figshare.com/files/844161"], "description"=>"<p>The helices of the pseudo-knotted known structure for the bacterial tmRNA are correctly predicted by Transat. Transat also predicts several additional helices, but the region of the tmRNA sequences that contains the reading frame which ends in a translation stop signal is devoid of statistically significant transient helices supporting the hypothesis that the sequence in this region in the 5′ half of the RNA has been chosen to remain single-stranded and readily accessible. RNAalifold P predicts only a few of the helices of the known pseudo-knotted structure and no additional structural features, see also <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1000823#pcbi-1000823-g015\" target=\"_blank\">Figure 15</a>. Please refer to the caption of <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1000823#pcbi-1000823-g016\" target=\"_blank\">Figure 16</a> for more information on arc-plots.</p>", "links"=>[], "tags"=>["bacterial"], "article_id"=>514622, "categories"=>["Medicine", "Evolutionary Biology", "Computational Biology", "Infectious Diseases", "Biophysics"], "users"=>["Nicholas J. P. Wiebe", "Irmtraud M. Meyer"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1000823.g020", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Comparison_of_T_ransat_top_figure_and_RNA_alifold_P_bottom_figure_for_the_bacterial_tmRNA_RF00023_/514622", "title"=>"Comparison of Transat (top figure) and RNAalifold P (bottom figure) for the bacterial tmRNA, RF00023.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-06-24 01:17:02"}

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