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Stanley, H. E.

Publications and source records attributed to Stanley, H. E..

30 records · Page 2

Fractal mechanisms and heart rate dynamics. Long-range correlations and their breakdown with disease

Under healthy conditions, the normal cardiac (sinus) interbeat interval fluctuates in a complex manner. Quantitative analysis using techniques adapted from statistical physics reveals the presence of long-range power-law correlations extending over thousands of heartbeats. This scale-invariant (fractal) behavior suggests that the regulatory system generating these fluctuations is operating far from equilibrium. In contrast, it is found that for subjects at high risk of sudden death (e.g., congestive heart failure patients), these long-range correlations break down. Application of fractal scaling analysis and related techniques provides new approaches to assessing cardiac risk and forecasting sudden cardiac death, as well as motivating development of novel physiologic models of systems that appear to be heterodynamic rather than homeostatic.

NASA Discipline Cardiopulmonary

Correlation approach to identify coding regions in DNA sequences

Recently, it was observed that noncoding regions of DNA sequences possess long-range power-law correlations, whereas coding regions typically display only short-range correlations. We develop an algorithm based on this finding that enables investigators to perform a statistical analysis on long DNA sequences to locate possible coding regions. The algorithm is particularly successful in predicting the location of lengthy coding regions. For example, for the complete genome of yeast chromosome III (315,344 nucleotides), at least 82% of the predictions correspond to putative coding regions; the algorithm correctly identified all coding regions larger than 3000 nucleotides, 92% of coding regions between 2000 and 3000 nucleotides long, and 79% of coding regions between 1000 and 2000 nucleotides. The predictive ability of this new algorithm supports the claim that there is a fundamental difference in the correlation property between coding and noncoding sequences. This algorithm, which is not species-dependent, can be implemented with other techniques for rapidly and accurately locating relatively long coding regions in genomic sequences.

Non-NASA Center

Statistical mechanics in biology: how ubiquitous are long-range correlations?

The purpose of this opening talk is to describe examples of recent progress in applying statistical mechanics to biological systems. We first briefly review several biological systems, and then focus on the fractal features characterized by the long-range correlations found recently in DNA sequences containing non-coding material. We discuss the evidence supporting the finding that for sequences containing only coding regions, there are no long-range correlations. We also discuss the recent finding that the exponent alpha characterizing the long-range correlations increases with evolution, and we discuss two related models, the insertion model and the insertion-deletion model, that may account for the presence of long-range correlations. Finally, we summarize the analysis of long-term data on human heartbeats (up to 10(4) heart beats) that supports the possibility that the successive increments in the cardiac beat-to-beat intervals of healthy subjects display scale-invariant, long-range "anti-correlations" (a tendency to beat faster is balanced by a tendency to beat slower later on). In contrast, for a group of subjects with severe heart disease, long-range correlations vanish. This finding suggests that the classical theory of homeostasis, according to which stable physiological processes seek to maintain "constancy," should be extended to account for this type of dynamical, far from equilibrium, behavior.

Non-NASA Center

Mosaic organization of DNA nucleotides

Long-range power-law correlations have been reported recently for DNA sequences containing noncoding regions. We address the question of whether such correlations may be a trivial consequence of the known mosaic structure ("patchiness") of DNA. We analyze two classes of controls consisting of patchy nucleotide sequences generated by different algorithms--one without and one with long-range power-law correlations. Although both types of sequences are highly heterogenous, they are quantitatively distinguishable by an alternative fluctuation analysis method that differentiates local patchiness from long-range correlations. Application of this analysis to selected DNA sequences demonstrates that patchiness is not sufficient to account for long-range correlation properties.

NASA Discipline Number 14-10

Generalized Levy-walk model for DNA nucleotide sequences

We propose a generalized Levy walk to model fractal landscapes observed in noncoding DNA sequences. We find that this model provides a very close approximation to the empirical data and explains a number of statistical properties of genomic DNA sequences such as the distribution of strand-biased regions (those with an excess of one type of nucleotide) as well as local changes in the slope of the correlation exponent alpha. The generalized Levy-walk model simultaneously accounts for the long-range correlations in noncoding DNA sequences and for the apparently paradoxical finding of long subregions of biased random walks (length lj) within these correlated sequences. In the generalized Levy-walk model, the lj are chosen from a power-law distribution P(lj) varies as lj(-mu). The correlation exponent alpha is related to mu through alpha = 2-mu/2 if 2 < mu < 3. The model is consistent with the finding of "repetitive elements" of variable length interspersed within noncoding DNA.

NASA Discipline Number 14-10

Finite-size effects on long-range correlations: implications for analyzing DNA sequences

We analyze the fluctuations in the correlation exponents obtained for noncoding DNA sequences. We find prominent sample-to-sample variations as well as variations within a single sample in the scaling exponent. To determine if these fluctuations may result from finite system size, we generate correlated random sequences of comparable length and study the fluctuations in this control system. We find that the DNA exponent fluctuations are consistent with those obtained from the control sequences having long-range power-law correlations. Finally, we compare our exponents for the DNA sequences with the exponents obtained from power-spectrum analysis and correlation-function techniques, and demonstrate that the original "DNA-walk" method is intrinsically more accurate due to reduced noise.

NASA Discipline Cardiopulmonary

Long-range anticorrelations and non-Gaussian behavior of the heartbeat

We find that the successive increments in the cardiac beat-to-beat intervals of healthy subjects display scale-invariant, long-range anticorrelations (up to 10 exp 4 heart beats). Furthermore, we find that the histogram for the heartbeat intervals increments is well described by a Levy (1991) stable distribution. For a group of subjects with severe heart disease, we find that the distribution is unchanged, but the long-range correlations vanish. Therefore, the different scaling behavior in health and disease must relate to the underlying dynamics of the heartbeat.

Peng, C.-K.

Fractal landscape analysis of DNA walks

By mapping nucleotide sequences onto a "DNA walk", we uncovered remarkably long-range power law correlations [Nature 356 (1992) 168] that imply a new scale invariant property of DNA. We found such long-range correlations in intron-containing genes and in non-transcribed regulatory DNA sequences, but not in cDNA sequences or intron-less genes. In this paper, we present more explicit evidences to support our findings.

NASA Program Space Physiology and Countermeasures

Fractal landscapes in biological systems: long-range correlations in DNA and interbeat heart intervals

Here we discuss recent advances in applying ideas of fractals and disordered systems to two topics of biological interest, both topics having common the appearance of scale-free phenomena, i.e., correlations that have no characteristic length scale, typically exhibited by physical systems near a critical point and dynamical systems far from equilibrium. (i) DNA nucleotide sequences have traditionally been analyzed using models which incorporate the possibility of short-range nucleotide correlations. We found, instead, a remarkably long-range power law correlation. We found such long-range correlations in intron-containing genes and in non-transcribed regulatory DNA sequences as well as intragenomic DNA, but not in cDNA sequences or intron-less genes. We also found that the myosin heavy chain family gene evolution increases the fractal complexity of the DNA landscapes, consistent with the intron-late hypothesis of gene evolution. (ii) The healthy heartbeat is traditionally thought to be regulated according to the classical principle of homeostasis, whereby physiologic systems operate to reduce variability and achieve an equilibrium-like state. We found, however, that under normal conditions, beat-to-beat fluctuations in heart rate display long-range power law correlations.

Non-NASA Center

Long-range correlations in nucleotide sequences

DNA sequences have been analysed using models, such as an n-step Markov chain, that incorporate the possibility of short-range nucleotide correlations. We propose here a method for studying the stochastic properties of nucleotide sequences by constructing a 1:1 map of the nucleotide sequence onto a walk, which we term a 'DNA walk'. We then use the mapping to provide a quantitative measure of the correlation between nucleotides over long distances along the DNA chain. Thus we uncover in the nucleotide sequence a remarkably long-range power law correlation that implies a new scale-invariant property of DNA. We find such long-range correlations in intron-containing genes and in nontranscribed regulatory DNA sequences, but not in complementary DNA sequences or intron-less genes.

NASA Discipline Cardiopulmonary

Inhomogeneous diffusion-limited aggregation

It is demonstrated here that inhomogeneous diffusion-limited aggregation (DLA) model can be used to simulate viscous fingering in a medium with inhomogeneous permeability and homogeneous porosity. The medium consists of a pipe-pore square-lattice network in which all pores have equal volume and the pipes have negligible volume. It is shown that fluctuations in a DLA-based growth process may be tuned by noise reduction, and that fluctuations in the velocity of the moving interface are multiplicative in form.

Selinger, Robin Blumberg

Tricritical points in multicomponent fluid mixtures

In view of experimental considerations, we give a model-independent argument that the novel tricritical points in multicomponent fluid mixtures, where three phases simultaneously become critical, are points on the boundary of a single two-dimensional surface of critical points. This result is corroborated by the Landau model suggested by Griffiths. The relationship between these tricritical points and the complex 'higher-order' critical points proposed to exist in certain magnetic systems is elucidated.

Hankey, A.