Simulação de MCI - AVL-BOOST - CONEMB-2017 - LRCancino - 03

Simulação de MCI - AVL-BOOST - CONEMB-2017 - LRCancino - 0

Bioinformatic analyses of mammalian 5'-UTR sequence properties of mRNAs predicts alternative translation initiation sites-2

D a set of 'if-then' rules that allowed the sequences containing the aTISs to be classified independently from sequences that do not possess aTISs. The critical parameters for the classification tree consisted of number of upstream AUGs, 5'-UTR length, consensus sequences (at positions-6/-7), the presence or absence of the Internal Ribosome Entry Site (IRES) structure, as well as G/C ratio.<p><b>Copyright information:</b></p><p>Taken from "Bioinformatic analyses of mammalian 5'-UTR sequence properties of mRNAs predicts alternative translation initiation sites"</p><p>http://www.biomedcentral.com/1471-2105/9/232</p><p>BMC Bioinformatics 2008;9():232-232.</p><p>Published online 8 May 2008</p><p>PMCID:PMC2396638.</p><p></p

Bioinformatic analyses of mammalian 5'-UTR sequence properties of mRNAs predicts alternative translation initiation sites-5

Categories. These annotations were compiled via BLAST searches and subsequent Gene Ontology (GO) and protein family analysis. The chart depicts the protein functions represented by the identified aTIS sequences. The functions of these proteins are significant for biological regulation.<p><b>Copyright information:</b></p><p>Taken from "Bioinformatic analyses of mammalian 5'-UTR sequence properties of mRNAs predicts alternative translation initiation sites"</p><p>http://www.biomedcentral.com/1471-2105/9/232</p><p>BMC Bioinformatics 2008;9():232-232.</p><p>Published online 8 May 2008</p><p>PMCID:PMC2396638.</p><p></p

Bioinformatic analyses of mammalian 5'-UTR sequence properties of mRNAs predicts alternative translation initiation sites-1

stack indicates the sequence conservation at that position, while the height of nucleotide symbols within the stack indicates the relative frequency of each base at that position. The start site is indicated at positions 1, 2, and 3. . The relative abundance of nucleotides (A, T, C, G) at aTISs is shown for a window of -10 to +10 bases at the initiation codon, with the aTIS start codon in positions 1, 2, and 3. Conservation around all of the alternative start sites aTISs is illustrated. Note the strong conservation of (G/C) at the -6 position and C at the -7 position. . Graphical representation of relative nucleotide abundances at AUG sites is shown for bases in the region of -10 to +10 bases relative to the initiation codon, with the AUG codon in positions 1, 2, and 3. Conservation at the -3 and +4 locations are consistent with traditional Kozak consensus sequence. These features are distinguished from that of thte aTIS sequences which show conservation at positions -6 and -7 (Figure 2A).<p><b>Copyright information:</b></p><p>Taken from "Bioinformatic analyses of mammalian 5'-UTR sequence properties of mRNAs predicts alternative translation initiation sites"</p><p>http://www.biomedcentral.com/1471-2105/9/232</p><p>BMC Bioinformatics 2008;9():232-232.</p><p>Published online 8 May 2008</p><p>PMCID:PMC2396638.</p><p></p

Bioinformatic analyses of mammalian 5'-UTR sequence properties of mRNAs predicts alternative translation initiation sites-4

Eural Networks are a computational algorithm that uses layers of neurons with weighted edges connecting each layer to perform classification. To determine the specific ANN architecture, this study started with a static training set and modified the number of neurons in the hidden layer of the ANN as well as the activation function used for the neurons in each layer. The resulting ANN contained 10 neurons in the input layer, 20 neurons in the hidden layer and a single output neuron. Inputs to the ANN are normalized in order to negate the effect of measurements in different ranges. The output neuron provides values in the range [0, 1].<p><b>Copyright information:</b></p><p>Taken from "Bioinformatic analyses of mammalian 5'-UTR sequence properties of mRNAs predicts alternative translation initiation sites"</p><p>http://www.biomedcentral.com/1471-2105/9/232</p><p>BMC Bioinformatics 2008;9():232-232.</p><p>Published online 8 May 2008</p><p>PMCID:PMC2396638.</p><p></p

Bioinformatic analyses of mammalian 5'-UTR sequence properties of mRNAs predicts alternative translation initiation sites-0

Categories. These annotations were compiled via BLAST searches and subsequent Gene Ontology (GO) and protein family analysis. The chart depicts the protein functions represented by the identified aTIS sequences. The functions of these proteins are significant for biological regulation.<p><b>Copyright information:</b></p><p>Taken from "Bioinformatic analyses of mammalian 5'-UTR sequence properties of mRNAs predicts alternative translation initiation sites"</p><p>http://www.biomedcentral.com/1471-2105/9/232</p><p>BMC Bioinformatics 2008;9():232-232.</p><p>Published online 8 May 2008</p><p>PMCID:PMC2396638.</p><p></p

Bioinformatic analyses of mammalian 5'-UTR sequence properties of mRNAs predicts alternative translation initiation sites-3

Rated in this figure. The alternative start site, CUG, is circled in red. Features of this secondary structure served as inputs to the ANN. For each 50 base pair window surrounding the putative alternative initiation site (as shown in this figure), the local stability of the start codon itself and the free energy of the structure were recorded. The window size (50 bp) was experimentally determined as the minimum window size which produced consistent foldings through shifts in the folding window. Based on the scale of 0 to 3 scale, the stability would be measured as a 3 since the codon (all three bases) are present entirely in the loop structure.<p><b>Copyright information:</b></p><p>Taken from "Bioinformatic analyses of mammalian 5'-UTR sequence properties of mRNAs predicts alternative translation initiation sites"</p><p>http://www.biomedcentral.com/1471-2105/9/232</p><p>BMC Bioinformatics 2008;9():232-232.</p><p>Published online 8 May 2008</p><p>PMCID:PMC2396638.</p><p></p

Table_1_Novel and reported compensatory mutations in rpoABC genes found in drug resistant tuberculosis outbreaks.XLSX

BackgroundRifampicin (RIF) is a key first-line drug used to treat tuberculosis, a primarily pulmonary disease caused by Mycobacterium tuberculosis. RIF resistance is caused by mutations in rpoB, at the cost of slower growth and reduced transcription efficiency. Antibiotic resistance to RIF is prevalent despite this fitness cost. Compensatory mutations in rpoABC genes have been shown to alleviate the fitness cost of rpoB:S450L, explaining how RIF resistant strains harbor this mutation can spread so rapidly. Unfortunately, the full set of RIF compensatory mutations is still unknown, particularly those compensating for rarer RIF resistance mutations.ObjectivesWe performed an association study on a globally representative set of 4,309 whole genome sequenced clinical M. tuberculosis isolates to identify novel putative compensatory mutations, determine the prevalence of known and previously reported putative compensatory mutations, and determine which RIF resistance markers associate with these compensatory mutations.Results and conclusionsOf the 1,079 RIF resistant isolates, 638 carried previously reported putative and high-probability compensatory mutations. Our strict criteria identified 46 additional mutations in rpoABC for which no strong prior evidence of their compensatory role exists. Of these, 35 have previously been reported. As such, our independent corroboration adds to the mounting evidence that these 35 also carry a compensatory role. The remaining 11 are novel putative compensatory markers, reported here for the first time. Six of these 11 novel putative compensatory mutations had two or more mutation events. Most compensatory mutations appear to be specifically compensating for the fitness loss due to rpoB:S450L. However, an outbreak of 22 closely related isolates each carried three rpoB mutations, the rare RIFR markers D435G and L452P and the putative compensatory mutation I1106T. This suggests compensation may require specific combinations of rpoABC mutations. Here, we report only mutations that met our very strict criteria. It is highly likely that many additional rpoABC mutations compensate for rare resistance-causing mutations and therefore did not carry the statistical power to be reported here. These findings aid in the identification of RIF resistant M. tuberculosis strains with restored fitness, which pose a greater risk of causing resistant outbreaks.</p

Minor subpopulation detection in two sputum samples from Moldova.

<p>Resistant and erroneous allele frequencies from three resistance SNP loci in the <i>inhA</i> promoter are shown. Patient 21–0067 with 0.05% resistant allele and patient 22–0129 with 11.39% resistant allele at <i>inhA</i> -15, compared to erroneous and resistant alleles below 0.01% at the other two SNP positions.</p

SMOR minor subpopulation examination of a single replicate of 7 mixtures at six known differing resistance SNP loci.

<p>Each circle represents the percent SMOR call, where color represents allele state, for a single sample at the six resistant SNP loci. All 36 SNP loci were examined; however the seven different mixtures contain six known allelic differences in resistant conferring SNP loci.</p