The Experts below are selected from a list of 327 Experts worldwide ranked by ideXlab platform
Kiyoshi Ezawa - One of the best experts on this subject based on the ideXlab platform.
-
general continuous time markov model of Sequence evolution via insertions deletions local alignment probability computation
BMC Bioinformatics, 2016Co-Authors: Kiyoshi EzawaAbstract:Background Insertions and deletions (indels) account for more nucleotide differences between two related DNA Sequences than substitutions do, and thus it is imperative to develop a method to reliably calculate the occurrence probabilities of Sequence alignments via evolutionary processes on an Entire Sequence. Previously, we presented a perturbative formulation that facilitates the ab initio calculation of alignment probabilities under a continuous-time Markov model, which describes the stochastic evolution of an Entire Sequence via indels with quite general rate parameters. And we demonstrated that, under some conditions, the ab initio probability of an alignment can be factorized into the product of an overall factor and contributions from regions (or local alignments) delimited by gapless columns.
-
general continuous time markov model of Sequence evolution via insertions deletions are alignment probabilities factorable
BMC Bioinformatics, 2016Co-Authors: Kiyoshi EzawaAbstract:Insertions and deletions (indels) account for more nucleotide differences between two related DNA Sequences than substitutions do, and thus it is imperative to develop a stochastic evolutionary model that enables us to reliably calculate the probability of the Sequence evolution through indel processes. Recently, indel probabilistic models are mostly based on either hidden Markov models (HMMs) or transducer theories, both of which give the indel component of the probability of a given Sequence alignment as a product of either probabilities of column-to-column transitions or block-wise contributions along the alignment. However, it is not a priori clear how these models are related with any genuine stochastic evolutionary model, which describes the stochastic evolution of an Entire Sequence along the time-axis. Moreover, currently none of these models can fully accommodate biologically realistic features, such as overlapping indels, power-law indel-length distributions, and indel rate variation across regions. Here, we theoretically dissect the ab initio calculation of the probability of a given Sequence alignment under a genuine stochastic evolutionary model, more specifically, a general continuous-time Markov model of the evolution of an Entire Sequence via insertions and deletions. Our model is a simple extension of the general “substitution/insertion/deletion (SID) model”. Using the operator representation of indels and the technique of time-dependent perturbation theory, we express the ab initio probability as a summation over all alignment-consistent indel histories. Exploiting the equivalence relations between different indel histories, we find a “sufficient and nearly necessary” set of conditions under which the probability can be factorized into the product of an overall factor and the contributions from regions separated by gapless columns of the alignment, thus providing a sort of generalized HMM. The conditions distinguish evolutionary models with factorable alignment probabilities from those without ones. The former category includes the “long indel” model (a space-homogeneous SID model) and the model used by Dawg, a genuine Sequence evolution simulator. With intuitive clarity and mathematical preciseness, our theoretical formulation will help further advance the ab initio calculation of alignment probabilities under biologically realistic models of Sequence evolution via indels.
Thomas E Creighton - One of the best experts on this subject based on the ideXlab platform.
-
effects of trifluoroethanol on the conformations of peptides representing the Entire Sequence of bovine pancreatic trypsin inhibitor
Biochemistry, 1995Co-Authors: Johan Kemmink, Thomas E CreightonAbstract:The effects of the cosolvent trifluoroethanol on the conformations of four peptides representing the Entire Sequence of bovine pancreatic trypsin inhibitor (BPTI) have been measured by CD and NMR. No substantial amounts of helical conformations were induced in one peptide with four proline residues dispersed throughout its Sequence, and there were no substantial effects on its average conformational properties or on the interactions between neighboring residues that are normally evident. The other three peptides became helical, although not completely, over their Entire lengths. There was a reasonable correlation between the induced content of alpha-helix and the predicted helical propensities of all four peptides. Only one of these peptides is helical in native BPTI; the other two are extended beta-strands. The latter two have an intrinsic propensity for helix formation, but a greater propensity for beta-sheet formation in folded proteins.
-
local conformations of peptides representing the Entire Sequence of bovine pancreatic trypsin inhibitor and their roles in folding
Journal of Molecular Biology, 1993Co-Authors: Johan Kemmink, Thomas E CreightonAbstract:The conformational properties of seven overlapping peptides, 9 to 16 residues long, that comprise the Entire primary structure of bovine pancreatic trypsin inhibitor (BPTI) have been characterized by circular dichroism and 1H nuclear magnetic resonance. The peptides are largely disordered, although apparently with somewhat different average conformational propensities of the polypeptide backbone, similar to those indicated by methods to predict secondary structure. Reduced BPTI appears to be approximately the sum of the individual peptides. Several local interactions involving aromatic rings of side-chains interacting with groups nearby in the primary structure have been identified and verified by replacing the responsible side-chains. The roles of these interactions in folding of reduced BPTI could be determined, as the conformational and nuclear magnetic resonance properties of all the major disulphide intermediates are known. Two of these local interactions contribute to the folding process and to stability of the fully folded conformation, whereas the other two do not.
Johan Kemmink - One of the best experts on this subject based on the ideXlab platform.
-
effects of trifluoroethanol on the conformations of peptides representing the Entire Sequence of bovine pancreatic trypsin inhibitor
Biochemistry, 1995Co-Authors: Johan Kemmink, Thomas E CreightonAbstract:The effects of the cosolvent trifluoroethanol on the conformations of four peptides representing the Entire Sequence of bovine pancreatic trypsin inhibitor (BPTI) have been measured by CD and NMR. No substantial amounts of helical conformations were induced in one peptide with four proline residues dispersed throughout its Sequence, and there were no substantial effects on its average conformational properties or on the interactions between neighboring residues that are normally evident. The other three peptides became helical, although not completely, over their Entire lengths. There was a reasonable correlation between the induced content of alpha-helix and the predicted helical propensities of all four peptides. Only one of these peptides is helical in native BPTI; the other two are extended beta-strands. The latter two have an intrinsic propensity for helix formation, but a greater propensity for beta-sheet formation in folded proteins.
-
local conformations of peptides representing the Entire Sequence of bovine pancreatic trypsin inhibitor and their roles in folding
Journal of Molecular Biology, 1993Co-Authors: Johan Kemmink, Thomas E CreightonAbstract:The conformational properties of seven overlapping peptides, 9 to 16 residues long, that comprise the Entire primary structure of bovine pancreatic trypsin inhibitor (BPTI) have been characterized by circular dichroism and 1H nuclear magnetic resonance. The peptides are largely disordered, although apparently with somewhat different average conformational propensities of the polypeptide backbone, similar to those indicated by methods to predict secondary structure. Reduced BPTI appears to be approximately the sum of the individual peptides. Several local interactions involving aromatic rings of side-chains interacting with groups nearby in the primary structure have been identified and verified by replacing the responsible side-chains. The roles of these interactions in folding of reduced BPTI could be determined, as the conformational and nuclear magnetic resonance properties of all the major disulphide intermediates are known. Two of these local interactions contribute to the folding process and to stability of the fully folded conformation, whereas the other two do not.
Norihiro Okada - One of the best experts on this subject based on the ideXlab platform.
-
determination of the Entire Sequence of turtle cr1 the first open reading frame of the turtle cr1 element encodes a protein with a novel zinc finger motif
Molecular Biology and Evolution, 1997Co-Authors: Masaki Kajikawa, Kazuhiko Ohshima, Norihiro OkadaAbstract:CR1 elements are a family of retroposons. They are classified as long interspersed elements (LINEs) or non-long-terminal-repeat (non-LTR) retrotransposons, and they have been found in the genomes of many vertebrates. However, they have been only partially characterized, and only a 2-kb region of the 3' end of chicken CR1 has been Sequenced. In the present study, we determined the Entire consensus Sequence of CR1 elements in the turtle genome, designated PsCR1. The first open reading frame (ORF1) of PsCR1 has two unusual arrangements of Cys residues. One of them includes a zinc finger motif, CX2CX14CX2C. The putative zinc finger has cysteine residues with identical spacing and a similar amino acid composition to those found in the species-specific transcription initiation factors SL1 and TIF-IB. The 5' untranslated region (5' UTR) of PsCR1 contains a Sequence similar to part of the human L1 promoter, L1 site A, and several cis elements of the type found in eukaryotic genes. Within a region of about 500 bp, there are nine "E boxes," cis elements that are recognized by the basic helix-loop-helix (bHLH) family of proteins. This observation raises the possibility that cellular transcription factors that bind to these Sequences might act in concert to regulate the expression of PsCR1. The extent of the Sequence divergence of the 3' UTR of CR1 between species was found to be lower than the rate of nonsynonymous substitutions per site in ORF2, suggesting that a strict functional constraint must exist for this region. This result strongly suggests that the conserved 3'-end Sequence of CR1 is the recognition site for the reverse transcriptase of CR1. A discussion is presented of a possible mechanism for the integration of CR1 elements and also of the intriguing possible recruitment of the reverse transcriptase for the retroposition of SINEs.
Masaki Kajikawa - One of the best experts on this subject based on the ideXlab platform.
-
determination of the Entire Sequence of turtle cr1 the first open reading frame of the turtle cr1 element encodes a protein with a novel zinc finger motif
Molecular Biology and Evolution, 1997Co-Authors: Masaki Kajikawa, Kazuhiko Ohshima, Norihiro OkadaAbstract:CR1 elements are a family of retroposons. They are classified as long interspersed elements (LINEs) or non-long-terminal-repeat (non-LTR) retrotransposons, and they have been found in the genomes of many vertebrates. However, they have been only partially characterized, and only a 2-kb region of the 3' end of chicken CR1 has been Sequenced. In the present study, we determined the Entire consensus Sequence of CR1 elements in the turtle genome, designated PsCR1. The first open reading frame (ORF1) of PsCR1 has two unusual arrangements of Cys residues. One of them includes a zinc finger motif, CX2CX14CX2C. The putative zinc finger has cysteine residues with identical spacing and a similar amino acid composition to those found in the species-specific transcription initiation factors SL1 and TIF-IB. The 5' untranslated region (5' UTR) of PsCR1 contains a Sequence similar to part of the human L1 promoter, L1 site A, and several cis elements of the type found in eukaryotic genes. Within a region of about 500 bp, there are nine "E boxes," cis elements that are recognized by the basic helix-loop-helix (bHLH) family of proteins. This observation raises the possibility that cellular transcription factors that bind to these Sequences might act in concert to regulate the expression of PsCR1. The extent of the Sequence divergence of the 3' UTR of CR1 between species was found to be lower than the rate of nonsynonymous substitutions per site in ORF2, suggesting that a strict functional constraint must exist for this region. This result strongly suggests that the conserved 3'-end Sequence of CR1 is the recognition site for the reverse transcriptase of CR1. A discussion is presented of a possible mechanism for the integration of CR1 elements and also of the intriguing possible recruitment of the reverse transcriptase for the retroposition of SINEs.