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PubMed2004

Coding and non-coding DNA thermal stability differences in eukaryotes studied by melting simulation, base shuffling and DNA nearest neighbor frequency analysis.

The melting of the coding and non-coding classes of natural DNA sequences was investigated using a program, MELTSIM, which simulates DNA melting based upon an empirically parameterized nearest neighbor thermodynamic model. We calculated T(m) results of 8144 natural sequences from 28 eukaryotic organisms of varying F(GC) (mole fraction of G and C) and of 3775 coding and 3297 non-coding sequences derived from those natural sequences. These data demonstrated that the T(m) vs. F(GC) relationships in coding and non-coding DNAs are both linear but have a statistically significant difference (6.6%) in their slopes. These relationships are significantly different from the T(m) vs. F(GC) relationship embodied in the classical Marmur-Schildkraut-Doty (MSD) equation for the intact long natural sequences. By analyzing the simulation results from various base shufflings of the original DNAs and the average nearest neighbor frequencies of those natural sequences across the F(GC) range, we showed that these differences in the T(m) vs. F(GC) relationships are largely a direct result of systematic F(GC)-dependent biases in nearest neighbor frequencies for those two different DNA classes. Those differences in the T(m) vs. F(GC) relationships and biases in nearest neighbor frequencies also appear between the sequences from multicellular and unicellular organisms in the same coding or non-coding classes, albeit of smaller but significant magnitudes.

Base Composition↗

PubMed2005

Do discharge codes underestimate hospitalisation due to heart failure? Validation study of hospital discharge coding for heart failure.

BACKGROUND: Discharge codes are frequently used to describe hospital activity related to heart failure (HF). OBJECTIVES: To determine whether discharge codes for HF underestimated or overestimated hospital activity related to HF. DESIGN: Patients with atrial fibrillation (AF), who commonly have HF, were identified and their case notes reviewed to identify cases of HF missed by discharge codes. PARTICIPANTS AND METHODS: Patients admitted between November 1997 and January 1998 with either HF or AF. Identification of HF and AF by ICD10 hospital discharge codes. Identification of additional cases of AF from a central hospital-wide ECG database. RESULTS: We identified 330 cases with an ICD 10 code for HF, of which 43 (13%) were deemed to be miscoded, 32 patients (10%) were classified as possible, 39 (12%) as probable and 216 (65%) as definite HF. Results were similar whether or not HF was the primary discharge diagnosis. We identified 452 patients with AF, of whom 45 (10%) were classified as probable and 193 (43%) as definite HF. 129 (54%) of these cases had no diagnostic discharge code for HF. ICD 10 discharge codes for HF were correct in 77% of cases but identified only 66% of patients with probable or definite HF in this analysis. Screening of other diagnoses would have identified further cases of HF. CONCLUSIONS: Hospital discharge codes substantially underestimate hospital events related to HF in the UK.

Aged↗

PubMed2000

The ability of a computer program based on the Marquette Matrix-12 short measurement matrix to replicate coding by the Minnesota ECG coding laboratory.

The study was undertaken to determine whether a computer program that uses "short measurement matrix" data from the Marquette Matrix-12 system can replicate Minnesota electrocardiogram (ECG) coding laboratory interpretations. An agreement was found between coding of median complex ECGs at the Minnesota ECG coding laboratory and coding based on Marquette Matrix-12 short measurement matrix. The comparison was based on 763 ECGs plus chest pain history and serum enzyme values for a stratified random sample of 141 patients hospitalized in 1990 or 1991 for an event coded as HICDA 410.x (acute myocardial infarction), 411 (other acute and subacute forms of ischemic heart disease), 413 (angina pectoris), or 796.9 (other ill defined and unknown causes of morbidity and mortality). The population was reconstructed from the stratified random sample to enable population-based inferences. Exact agreement between Matrix-12 and Minnesota coding laboratory interpretation on 4 ECG patterns (evolving diagnostic, diagnostic, equivocal, or other ECG pattern) was 74.5% (Kappa = 0.63 +/- 0.05) for the stratified random sample and 78.8% (Kappa = 0.66 +/- 0.05) for the reconstructed population. For coding myocardial infarction based on the ECG, serum enzyme levels, and ischemic chest pain, agreement was 91.5% (Kappa = 0.85 +/- 0.04) for the stratified random sample and 90% (Kappa = 0.83 +/- 0.04) for the reconstructed population. Although ECG interpretation by a computer program based on the short measurement matrix of the Matrix 12 system results in better agreement than prior attempts to replicate the Minnesota coding laboratory, interpretation remains unacceptably discordant.

Angina Pectoris↗

PubMed2005

Identification of coding and non-coding sequences using local Holder exponent formalism.

MOTIVATION: Accurate prediction of genes in genomes has always been a challenging task for bioinformaticians and computational biologists. The discovery of existence of distinct scaling relations in coding and non-coding sequences has led to new perspectives in the understanding of the DNA sequences. This has motivated us to exploit the differences in the local singularity distributions for characterization and classification of coding and non-coding sequences. RESULTS: The local singularity density distribution in the coding and non-coding sequences of four genomes was first estimated using the wavelet transform modulus maxima methodology. Support vector machines classifier was then trained with the extracted features. The trained classifier is able to provide an average test accuracy of 97.7%. The local singularity features in a DNA sequence can be exploited for successful identification of coding and non-coding sequences. CONTACT: Available on request from bd.kulkarni@ncl.res.in.

Algorithms↗

PubMed1990

Coding external causes of injury (E-codes) in Maryland hospital discharges 1979-88: a statewide study to explore the uncoded population.

We examined the trends in hospital discharge E-coding in Maryland over a 10-year period. The overall proportion of E-coded discharges has increased from 40 percent in 1979 to 55 percent in 1988. E-coding was lower in the severely injured, the elderly, and patients with long hospital stays. Our findings demonstrate that E-code reporting varies because of the limited number of data fields available for coding of discharge diagnoses. Universal, systematic reporting of E-codes in hospital discharge data is essential if these data are to provide critically needed information about nonfatal injuries. Hospital discharge data formats should contain separate fields for E-codes and the use of these codes, we believe, should be mandated.

Age Factors↗

PubMed1997

The effects of automated encoders on coding accuracy and coding speed.

Encoded data on diagnoses and procedures are put to a broad range of uses. Coding accuracy and speed are imperative. One method that coding experts have recommended to improve coding accuracy and speed is automated encoders. The article describes the effect of automated encoders on coding accuracy and speed when used by trained coding staff. A study involving six Veterans Administration medical centers found that, overall, coding accuracy improved 19.4 percent after implementation of encoding software. The effect on coding speed, however, depended on the system set-up, with some set-ups actually reducing the number of discharges coded per day.

Abstracting and Indexing↗

PubMed1996

A complementary circular code in the protein coding genes.

Recently, shifted periodicities 1 modulo 3 and 2 modulo 3 have been identified in protein (coding) genes of both prokaryotes and eukaryotes with autocorrelation functions analysing eight of 64 trinucleotides (Arquès et al., 1995). This observation suggests that the trinucleotides are associated with frames in protein genes. In order to verify this hypothesis, a distribution of the 64 trinucleotides AAA,..., TTT is studied in both gene populations by using a simple method based on the trinucleotide frequencies per frame. In protein genes, the trinucleotides can be read in three frames: the reading frame 0 established by the ATG start trinucleotide and frame 1 (resp. 2) which is the frame 0 shifted by 1 (resp. 2) nucleotide in the 5'-3' direction. Then, the occurrence frequencies of the 64 trinucleotides are computed in the three frames. By classifying each of the 64 trinucleotides in its preferential occurrence frame, i.e. the frame associated with its highest frequency, three subsets of trinucleotides can be identified in the three frames. This approach is applied in the two gene populations. Unexpectedly, the same three subsets of trinucleotides are identified in these two gene populations: Tzero = Xzero [symbol: see text] {AAA,TTT} with Xzero = {AAC,AAT,ACC,ATC,ATT, CAG,CTC,CTG,GAA,GAC,GAG, GAT,GCC,GGC,GGT,GTA,GTC,GTT,TAC,TTC} in frame 0, T1 = X1 [symbol: see text] {CCC} in frame 1 and T2 = X2 [symbol: see text] {GGG} in frame 2, each subset Xzero, X1 and X2 having 20 trinucleotides. Surprisingly, these three subsets have five important properties: (i) the property of maximal circular code for Xzero (resp. X1, X2) allowing the automatical retrieval of frame 0 (resp. 1, 2) in any region of a protein gene model (formed by a series of trinucleotides of Xzero) without using a start codon; (ii) the DNA complementarity property C (e.g. C(AAC) = GTT): C(T0) = T0, C(T1) = T2 and C(T2) = T1 allowing the two paired reading frames of a DNA double helix simultaneously to code for amino acids; (iii) the circular permutation property P (e.g. P(AAC) = ACA): P(Xzero) = X1 and P(X1) = X2 implying that the two subsets X1 and X2 can be deduced from Xzero; (iv) the rarity property with an occurrence probability of Xzero equal to 6 x 10(-8); and (v) the concatenation property with: a high frequency (27.5%) of misplaced trinucleotides in the shifted frames, a maximum (13 nucleotides) length of the minimal window to automatically retrieve the frame and an occurrence of the four types of nucleotides in the three trinucleotides sites, in favour of an evolutionary code. In the Discussion, the identified subsets Tzero, T1 and T2 replaced in the three two-letter genetic alphabets purine/pyrimidine, amino/ceto and strong/weak interaction, allow us to deduce that the RNY model (R = purine = A or G, Y = pyrimidine = C or T, N = R or Y) (Eigen & Schuster, 1978) is the closest two-letter codon model to the trinucleotides of Tzero. Then, these three subsets are related to the genetic code. The trinucleotides of Tzero code for 13 amino acids: Ala, Asn, Asp, Gln, Glu, Gly, Ile, Leu, Lys, Phe, Thr, Tyr and Val. Finally, a strong correlation between the usage of the trinucleotides of Tzero in protein genes and the amino acid frequencies in proteins is observed as six among seven amino acids not coded by Tzero, have as expected the lowest frequencies in proteins of both prokaryotes and eukaryotes.

Amino Acids↗

PubMed2005

A fractal method to distinguish coding and non-coding sequences in a complete genome based on a number sequence representation.

A fractal method to distinguish coding and non-coding sequences in a complete genome is proposed, based on different statistical behaviors between these two kinds of sequences. We first propose a number sequence representation of DNA sequences. Multifractal analysis is then performed on the measure representation of the obtained number sequence. The three exponents C(-1), C1 and C2 are selected from the result of multifractal analysis. Each DNA may be represented by a point in the three-dimensional space generated by these three-component vectors. It is shown that points corresponding to coding and non-coding sequences in the complete genome of many prokaryotes are roughly distributed in different regions. Fisher's discriminant algorithm can be used to separate these two regions in the spanned space. If the point (C(-1),C1,C2) for a DNA sequence is situated in the region corresponding to coding sequences, the sequence is discriminated as a coding sequence; otherwise, the sequence is classified as a non-coding one. For all 51 prokaryotes we considered , the average discriminant accuracies pc,pnc,qc and qnc reach 72.28%, 84.65%, 72.53% and 84.18%, respectively.

Animals↗

PubMed1997

A code in the protein coding genes.

A statistical analysis with 12,288 autocorrelation functions applied in protein (coding) genes of prokaryotes and eukaryotes identifies three subsets of trinucleotides in their three frames: T0 = X0 [symbol: see text] {AAA, TTT} with X0 = {AAC, AAT, ACC, ATC, ATT, CAG, CTC, CTG, GAA, GAC, GAG, GAT, GCC, GGC, GGT, GTA, GTC, GTT, TAC, TTC} in frame 0 (the reading frame established by the ATG start trinucleotide), T1 = X1 [symbol: see text] {CCC} in frame 1 and T2 = X2 [symbol: see text] {GGG} in frame 2 (the frames 1 and 2 being the frame 0 shifted by one and two nucleotides, respectively, to the right). These three subsets are identical in these two gene populations and have five important properties: (i) the property of maximal (20 trinucleotides) circular code for X0 (resp. X1, X2) allowing to retrieve automatically the frame 0 (resp. 1, 2) in any region of the gene without start codon; (ii) the DNA complementarity property C (e.g. C(AAC) = GTT): C(T0) = T0, C(T1) = T2 and C(T2) = T1 allowing the two paired reading frames of a DNA double helix simultaneously to code for amino acids; (iii) the circular permutation property P (e.g. P(AAC) = ACA): P(X0) = X1 and P(X1) = X2 implying that the two subsets X1 and X2 can be deduced from X0; (iv) the rarity property with an occurrence probability of X0 = 6 x 10(-8); and (v) the concatenation properties in favour of an evolutionary code: a high frequency (27.5%) of misplaced trinucleotides in the shifted frames, a maximum (13 nucleotides) length of the minimal window to retrieve automatically the frame and an occurrence of the four types of nucleotides in the three trinucleotide sites. In Discussion, a simulation based on an independent mixing of the trinucleotides of T0 allows to retrieve the two subsets T1 and T2. Then, the identified subsets T0, T1 and T2 replaced in the 2-letter genetic alphabet {R, Y} (R = purine = A or G, Y = pyrimidine = C or T) allow to retrieve the RNY model (N = R or Y) and to explain previous works in the alphabet {R, Y}. Then, these three subsets are related to the genetic code. The trinucleotides of T0 code for 13 amino acids: Ala, Asn, Asp, Gln, Glu, Gly, Ile, Leu, Lys, Phe, Thr, Tyr and Val. Finally, a strong correlation between the usage of the trinucleotides of T0 in protein genes and the amino acid frequencies in proteins is observed as six among seven amino acids not coded by T0, have as expected the lowest frequencies in proteins of both prokaryotes and eukaryotes.

Animals↗

PubMed1996

The genetic code and cyclic codes.

We proposed previously a cyclic code made of 22 triplets, which we now call the AB code. It is made up of the following chain: AUGGUGCCAUUCAAGACUAUGA. The letters A, U, C, G represent the classical symbols of the (purine and pyrimidine) bases of the genetic code. This chain presents the following features: (1) when it is in cyclic form, it begins with the initiation codon AUG, ends with the termination codon UGA, and it can be read triplet after triplet by choosing 1 and only 1 representative of each synonymy class in the classical degenerate genetic code made of 64 triplets. The chain, therefore, possesses 1 and only 1 codon for each amino-acid; (2) except for the doublet CG, triplets of the chain begin with the 15 other possible doublets of bases (satisfying the "wobble" hypothesis presented by Crick); (3) it corresponds (except for 1 base) to the "loop" part of the CEnothera mitochondrial Gly-tRNA; (4) it can be modified, without loss of the properties (1) and (2), in such a way as to have 15 bases in common with the loop part of other mitochondrial tRNA's considered as primitive, like Ala-, Pro- and Arg-tRNA; (5) it contains the most frequent triplets, but not the most rare ones, appearing in the genome of numerous species; (6) it exhibits a coherent internal structure with respect to the molecular weight of its triplets. This structure, also found in the loop part of mitochondrial tRNA's, contains an excess of AU bases with respect to GC bases. This fact has no explanation in the classical probabilistic model of the tRNA's. Therefore, we propose the cyclic AB code as a primitive genetic structure with the essential coding properties of the present genetic code.

Codon↗

PubMed2000

Distributions of dimeric tandem repeats in non-coding and coding DNA sequences.

We study the length distribution functions for the 16 possible distinct dimeric tandem repeats in DNA sequences of diverse taxonomic partitions of GenBank (known human and mouse genomes, and complete genomes of Caenorhabditis elegans and yeast). For coding DNA, we find that all 16 distribution functions are exponential. For non-coding DNA, the distribution functions for most of the dimeric repeats have surprisingly long tails, that fit a power-law function. We hypothesize that: (i) the exponential distributions of dimeric repeats in protein coding sequences indicate strong evolutionary pressure against tandem repeat expansion in coding DNA sequences; and (ii) long tails in the distributions of dimers in non-coding DNA may be a result of various mutational mechanisms. These long, non-exponential tails in the distribution of dimeric repeats in non-coding DNA are hypothesized to be due to the higher tolerance of non-coding DNA to mutations. By comparing genomes of various phylogenetic types of organisms, we find that the shapes of the distributions are not universal, but rather depend on the specific class of species and the type of a dimer.

Animals↗

PubMed1995

Asymmetric processing of coding ends and the effect of coding end nucleotide composition on V(D)J recombination.

The products of V(D)J recombination are coding and signal joints. We show that the nucleotide composition of the coding ends affects V(D)J recombination. The presence of Ts at the 5' end of either the 12 mer or the 23 mer recombination signal sequence (RSS) greatly decreases coding and signal joint formation, and Ts at the 5' ends of both RSSs eliminate recombination, suggesting that a step during the initiation phase of the recombination is affected. A 5' T coding end can be rescued it the other end contains 5' G, C, or A, implying that synapsis may be required. Furthermore, the presence of As at the 5' end of the 12 mer, but not the 23 mer, RSS affects coding but not signal joint formation. This observation of asymmetric processing of coding ends suggests that different protein complexes are bound to the two RSSs, and become transferred to the aligned coding ends during processing.

B-Lymphocytes↗

PubMed2002

A review of Anglo-American forensic professional codes of ethics with considerations for code design.

Continuing instances of ethical misconduct and recent advances in the practice of forensic science, the latter reflected by increased growth and professionalism, along with heightening public scrutiny, require that the profession be clear, current, and forthright about its core values. A way of expressing these values is through the codes of ethics of its professional membership organizations. Codes of ethics/conduct from 14 Anglo-American professional forensic membership organizations are reviewed for their clarity, construction, cogency, and the normative form of their provisions. Ethical precepts from the forensic codes reviewed are organized, in summary fashion, by obligation form and application context. Functions that professional codes have served in other professions are described. The codes are found to vary considerably. Some provisions are unclear, and most of the codes are less than comprehensive. There is very little guidance for application of ethical obligations in any of the codes reviewed. Suggestions for redesign, with a partial example, are provided.

Ethics, Medical↗

PubMed2002

Role of experience and oscillations in transforming a rate code into a temporal code.

In the vast majority of brain areas, the firing rates of neurons, averaged over several hundred milliseconds to several seconds, can be strongly modulated by, and provide accurate information about, properties of their inputs. This is referred to as the rate code. However, the biophysical laws of synaptic plasticity require precise timing of spikes over short timescales (<10 ms). Hence it is critical to understand the physiological mechanisms that can generate precise spike timing in vivo, and the relationship between such a temporal code and a rate code. Here we propose a mechanism by which a temporal code can be generated through an interaction between an asymmetric rate code and oscillatory inhibition. Consistent with the predictions of our model, the rate and temporal codes of hippocampal pyramidal neurons are highly correlated. Furthermore, the temporal code becomes more robust with experience. The resulting spike timing satisfies the temporal order constraints of hebbian learning. Thus, oscillations and receptive field asymmetry may have a critical role in temporal sequence learning.

Action Potentials↗

PubMed1998

The area code hypothesis revisited: olfactory receptors and other related transmembrane receptors may function as the last digits in a cell surface code for assembling embryos.

Recent evidence emerging from several laboratories, integrated with new data obtained by searching the genome databases, suggests that the area code hypothesis provides a good heuristic model for explaining the remarkable specificity of cell migration and tissue assembly that occurs throughout embryogenesis. The area code hypothesis proposes that cells assemble organisms, including their brains and nervous systems, with the aid of a molecular-addressing code that functions much like the country, area, regional, and local portions of the telephone dialing system. The complexity of the information required to code cells for the construction of entire organisms is so enormous that we assume that the code must make combinatorial use of members of large multigene families. Such a system would reuse the same receptors as molecular digits in various regions of the embryo, thus greatly reducing the total number of genes required. We present the hypothesis that members of the very large families of olfactory receptors and vomeronasal receptors fulfill the criteria proposed for area code molecules and could serve as the last digits in such a code. We discuss our evidence indicating that receptors of these families are expressed in many parts of developing embryos and suggest that they play a key functional role in cell recognition and targeting not only in the olfactory system but also throughout the brain and numerous other organs as they are assembled.

Animals↗

PubMed1993

V(D)J recombination coding junction formation without DNA homology: processing of coding termini.

Coding junction formation in V(D)J recombination generates diversity in the antigen recognition structures of immunoglobulin and T-cell receptor molecules by combining processes of deletion of terminal coding sequences and addition of nucleotides prior to joining. We have examined the role of coding end DNA composition in junction formation with plasmid substrates containing defined homopolymers flanking the recombination signal sequence elements. We found that coding junctions formed efficiently with or without terminal DNA homology. The extent of junctional deletion was conserved independent of coding ends with increased, partial, or no DNA homology. Interestingly, G/C homopolymer coding ends showed reduced deletion regardless of DNA homology. Therefore, DNA homology cannot be the primary determinant that stabilizes coding end structures for processing and joining.

Animals↗

PubMed1995

Influence of coding-end sequence on coding-end processing in V(D)J recombination.

The large diversity of the Ig and TCR repertoires is accounted for by combinatorial assembly of the germ-line-encoded V, D, and J gene segments, as well as extensive modification at the junctions during the recombination process. Those modifications, termed coding-end processing, consist of removal and addition of an apparently random number of nucleotides. To obtain further insights into the mechanism of the coding-end processing, we constructed a large data base of several Ig and TCR coding ends obtained in vivo, using conditions that avoid potential bias by cellular selection events. We show that the processing patterns are not random, but rather specific for each coding end, suggesting that specific motifs in the coding-end sequence influence the processing. We found a good correlation between the presence of internal stretches of at least three A.T nucleotides, absence of stretches of G.C nucleotides, and high average nucleotide deletion. Based on a detailed analysis of the processing patterns, we propose that nicks of the hairpin intermediate take place preferentially in potential open structures formed by weaker pairings of A.T stretches. Together, these findings indicate that the sequence of the coding end plays an important role in nonrandom aspects of the recombination mechanism. This suggests that coding-end sequences might have been selected throughout evolution to participate in an early control of the development of the primary repertoire.

Animals↗

PubMed1995

Complementary coding conforms to the primeval comma-less code.

The hypothesis that the universal genetic code is adapted to double-strand coding is supported by its remarkable compatibility with the RNY comma-less hypothesis. Coding by a triplet code on a polynucleotide double-strand allows for enciphering of five additional messages with reference to a chosen primary reading frame. Assuming the acceptance of coupled mutations on both strands, the best codon register for two overlapping messages can be inferred. The idea of evolutionarily compatible coding of two proteins by one nucleotide double-strand is extended to complementary coding for one protein in folded, single-stranded RNA.

Animals↗