Marcelo Magnasco - Academia.edu (original) (raw)
Papers by Marcelo Magnasco
Physical review. E, Statistical, nonlinear, and soft matter physics, 2015
Transport networks play a key role across four realms of eukaryotic life: slime molds, fungi, pla... more Transport networks play a key role across four realms of eukaryotic life: slime molds, fungi, plants, and animals. In addition to the developmental algorithms that build them, many also employ adaptive strategies to respond to stimuli, damage, and other environmental changes. We model these adapting network architectures using a generic dynamical system on weighted graphs and find in simulation that these networks ultimately develop a hierarchical organization of the final weighted architecture accompanied by the formation of a system-spanning backbone. In addition, we find that the long term equilibration dynamics exhibit behavior reminiscent of glassy systems characterized by long periods of slow changes punctuated by bursts of reorganization events.
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 29, 2015
What aspects of neuronal activity distinguish the conscious from the unconscious brain? This has ... more What aspects of neuronal activity distinguish the conscious from the unconscious brain? This has been a subject of intense interest and debate since the early days of neurophysiology. However, as any practicing anesthesiologist can attest, it is currently not possible to reliably distinguish a conscious state from an unconscious one on the basis of brain activity. Here we approach this problem from the perspective of dynamical systems theory. We argue that the brain, as a dynamical system, is self-regulated at the boundary between stable and unstable regimes, allowing it in particular to maintain high susceptibility to stimuli. To test this hypothesis, we performed stability analysis of high-density electrocorticography recordings covering an entire cerebral hemisphere in monkeys during reversible loss of consciousness. We show that, during loss of consciousness, the number of eigenmodes at the edge of instability decreases smoothly, independently of the type of anesthetic and speci...
BMC genomics, 2005
Microarray studies of the same phenomenon in different labs often appear at variance because the ... more Microarray studies of the same phenomenon in different labs often appear at variance because the published lists of regulated transcripts have disproportionately small intersections. We demonstrate that comparing studies by intersecting lists in this manner is methodologically flawed by reanalyzing three studies of the molecular signature of "stemness" in human embryonic stem cells. There are only 7 genes common to all three published lists, suggesting disagreement. Carefully reanalyzing all three together from the raw data we detect 111 genes upregulated and 95 downregulated in all three studies. The upregulated list was subject to rtRTPCR analysis and 75% of the genes were confirmed. Our findings show that the three studies have a substantial core of common genes, which is missed if only the published lists are examined. Combined analysis of multiple experiments can be a powerful way to distil coherent conclusions.
Physical review letters, Jan 26, 2009
It is widely recognized that balancing excitation and inhibition is important in the nervous syst... more It is widely recognized that balancing excitation and inhibition is important in the nervous system. When such a balance is sought by global strategies, few modes remain poised close to instability, and all other modes are strongly stable. Here we present a simple abstract model in which this balance is sought locally by units following "anti-Hebbian" evolution: all degrees of freedom achieve a close balance of excitation and inhibition and become "critical" in the dynamical sense. At long time scales, a complex "breakout" dynamics ensues in which different modes of the system oscillate between prominence and extinction; the model develops various long-tailed statistical behaviors and may become self-organized critical.
PloS one, 2012
Records of excitatory postsynaptic currents (EPSCs) are often complex, with overlapping signals t... more Records of excitatory postsynaptic currents (EPSCs) are often complex, with overlapping signals that display a large range of amplitudes. Statistical analysis of the kinetics and amplitudes of such complex EPSCs is nonetheless essential to the understanding of transmitter release. We therefore developed a maximum-likelihood blind deconvolution algorithm to detect exocytotic events in complex EPSC records. The algorithm is capable of characterizing the kinetics of the prototypical EPSC as well as delineating individual release events at higher temporal resolution than other extant methods. The approach also accommodates data with low signal-to-noise ratios and those with substantial overlaps between events. We demonstrated the algorithm's efficacy on paired whole-cell electrode recordings and synthetic data of high complexity. Using the algorithm to align EPSCs, we characterized their kinetics in a parameter-free way. Combining this approach with maximum-entropy deconvolution, we...
Genome biology, 2002
High-density oligonucleotide arrays (HDONAs) are a powerful tool for assessing differential mRNA ... more High-density oligonucleotide arrays (HDONAs) are a powerful tool for assessing differential mRNA expression levels. To establish the statistical significance of an observed change in expression, one must take into account the noise introduced by the enzymatic and hybridization steps, called type I noise. We undertake an empirical characterization of the experimental repeatability of results by carrying out statistical analysis of a large number of duplicate HDONA experiments. We assign scoring functions for expression ratios and associated quality measures. Both the perfect-match (PM) probes and the differentials between PM and single-mismatch (MM) probes are considered as raw intensities. We then calculate the log-ratio of the noise structure using robust estimates of their intensity-dependent variance. The noise structure in the log-ratios follows a local log-normal distribution in both the PM and PM-MM cases. Significance relative to the type I noise can therefore be quantified r...
Genome biology, 2002
High-density oligonucleotide microarrays provide a powerful tool for assessing differential mRNA ... more High-density oligonucleotide microarrays provide a powerful tool for assessing differential mRNA expression levels. Characterizing the noise resulting from the enzymatic and hybridization steps, called type I noise, is essential for attributing significance measures to the differential expression scores. We introduce scoring functions for expression ratios, and associated quality measures. Both the PM (Perfect Match) probes and PM-MM differentials (MM is the single MisMatch) are considered as raw intensities. We then characterize the log-ratio noise structure using robust estimates of their intensity dependent variance. We show the relationships between the obtained ratios and their quality measures. The complementarity of PM and PM-MM methods is emphasized by the probe sets signal to noise measures. Using a large set of replicate experiments, we demonstrate that the noise structure in the log-ratios very closely follows a local log-normal distribution for both the PM and PM-MM case...
Physical review. E, Statistical, nonlinear, and soft matter physics, 2001
The enzymes that pass DNA through DNA so as to remove entanglements, adenosine-triphosphate-hydro... more The enzymes that pass DNA through DNA so as to remove entanglements, adenosine-triphosphate-hydrolyzing type-II topoisomerases, are able to suppress the probability of self-entanglements (knots) and mutual entanglements (links) between approximately 10 kb plasmids, well below the levels expected, given the assumption that the topoisomerases pass DNA segments at random by thermal motion. This implies that a 10-nm type-II topoisomerase can somehow sense the topology of a large DNA. We previously introduced a "kinetic proofreading" model which supposes the enzyme to require two successive collisions in order to allow exchange of DNA segments, and we showed how it could quantitatively explain the reduction in knotting and linking complexity. Here we show how the same model quantitatively explains the reduced variance of the double-helix linking number (supercoiling) distribution observed experimentally.
Physical review. E, Statistical physics, plasmas, fluids, and related interdisciplinary topics, 2000
We describe a form of memory exhibited by extended excitable systems driven by stochastic fluctua... more We describe a form of memory exhibited by extended excitable systems driven by stochastic fluctuations. Under such conditions, the system self-organizes into a state characterized by power-law correlations, thus retaining long-term memory of previous states. The exponents are robust and model independent. We discuss implications of these results for the functioning of cortical neurons as well as for networks of neurons.
Nature, Jan 28, 1999
Cells must remove all entanglements between their replicated chromosomal DNAs to segregate them d... more Cells must remove all entanglements between their replicated chromosomal DNAs to segregate them during cell division. Entanglement removal is done by ATP-driven enzymes that pass DNA strands through one another, called type II topoisomerases. In vitro, some type II topoisomerases can reduce entanglements much more than expected, given the assumption that they pass DNA segments through one another in a random way. These type II topoisomerases (of less than 10 nm in diameter) thus use ATP hydrolysis to sense and remove entanglements spread along flexible DNA strands of up to 3,000 nm long. Here we propose a mechanism for this, based on the higher rate of collisions along entangled DNA strands, relative to collision rates on disentangled DNA strands. We show theoretically that if a type II topoisomerase requires an initial 'activating' collision before a second strand-passing collision, the probability of entanglement may be reduced to experimentally observed levels. This propo...
Physical review. E, Statistical physics, plasmas, fluids, and related interdisciplinary topics, 1994
Physical review. E, Statistical physics, plasmas, fluids, and related interdisciplinary topics, 1995
Physical review. E, Statistical physics, plasmas, fluids, and related interdisciplinary topics, 1993
Genome research, 2003
Although mRNA decay rates are a key determinant of the steady-state concentration for any given m... more Although mRNA decay rates are a key determinant of the steady-state concentration for any given mRNA species, relatively little is known, on a population level, about what factors influence turnover rates and how these rates are integrated into cellular decisions. We decided to measure mRNA decay rates in two human cell lines with high-density oligonucleotide arrays that enable the measurement of decay rates simultaneously for thousands of mRNA species. Using existing annotation and the Gene Ontology hierarchy of biological processes, we assign mRNAs to functional classes at various levels of resolution and compare the decay rate statistics between these classes. The results show statistically significant organizational principles in the variation of decay rates among functional classes. In particular, transcription factor mRNAs have increased average decay rates compared with other transcripts and are enriched in "fast-decaying" mRNAs with half-lives <2 h. In contrast,...
Physics Letters A, 1996
In biological evolution, the rate of mutations is "encoded" by enzymes which can be mutated like ... more In biological evolution, the rate of mutations is "encoded" by enzymes which can be mutated like any other gene. Inspired by this feature, we present a simple Brownian motion model, in which the temperature itself is a dynamical variable. Intrawell and interwell relaxations occur at different "temperatures" and have different dynamics, and the Kramers time becomes asymptotically linear in the barrier height for large heights.
BACKGROUND: The distribution of chromatin-associated proteins plays a key role in directing nucle... more BACKGROUND: The distribution of chromatin-associated proteins plays a key role in directing nuclear function. Previously, we developed an image-based method to quantify the nuclear distributions of proteins and showed that these distributions depended on the phenotype of human mammary epithelial cells. Here we describe a method that creates a hierarchical tree of the given cell phenotypes and calculates the statistical significance between them, based on the clustering analysis of nuclear protein distributions. RESULTS ...
Physical review. E, Statistical, nonlinear, and soft matter physics, 2015
Transport networks play a key role across four realms of eukaryotic life: slime molds, fungi, pla... more Transport networks play a key role across four realms of eukaryotic life: slime molds, fungi, plants, and animals. In addition to the developmental algorithms that build them, many also employ adaptive strategies to respond to stimuli, damage, and other environmental changes. We model these adapting network architectures using a generic dynamical system on weighted graphs and find in simulation that these networks ultimately develop a hierarchical organization of the final weighted architecture accompanied by the formation of a system-spanning backbone. In addition, we find that the long term equilibration dynamics exhibit behavior reminiscent of glassy systems characterized by long periods of slow changes punctuated by bursts of reorganization events.
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 29, 2015
What aspects of neuronal activity distinguish the conscious from the unconscious brain? This has ... more What aspects of neuronal activity distinguish the conscious from the unconscious brain? This has been a subject of intense interest and debate since the early days of neurophysiology. However, as any practicing anesthesiologist can attest, it is currently not possible to reliably distinguish a conscious state from an unconscious one on the basis of brain activity. Here we approach this problem from the perspective of dynamical systems theory. We argue that the brain, as a dynamical system, is self-regulated at the boundary between stable and unstable regimes, allowing it in particular to maintain high susceptibility to stimuli. To test this hypothesis, we performed stability analysis of high-density electrocorticography recordings covering an entire cerebral hemisphere in monkeys during reversible loss of consciousness. We show that, during loss of consciousness, the number of eigenmodes at the edge of instability decreases smoothly, independently of the type of anesthetic and speci...
BMC genomics, 2005
Microarray studies of the same phenomenon in different labs often appear at variance because the ... more Microarray studies of the same phenomenon in different labs often appear at variance because the published lists of regulated transcripts have disproportionately small intersections. We demonstrate that comparing studies by intersecting lists in this manner is methodologically flawed by reanalyzing three studies of the molecular signature of "stemness" in human embryonic stem cells. There are only 7 genes common to all three published lists, suggesting disagreement. Carefully reanalyzing all three together from the raw data we detect 111 genes upregulated and 95 downregulated in all three studies. The upregulated list was subject to rtRTPCR analysis and 75% of the genes were confirmed. Our findings show that the three studies have a substantial core of common genes, which is missed if only the published lists are examined. Combined analysis of multiple experiments can be a powerful way to distil coherent conclusions.
Physical review letters, Jan 26, 2009
It is widely recognized that balancing excitation and inhibition is important in the nervous syst... more It is widely recognized that balancing excitation and inhibition is important in the nervous system. When such a balance is sought by global strategies, few modes remain poised close to instability, and all other modes are strongly stable. Here we present a simple abstract model in which this balance is sought locally by units following "anti-Hebbian" evolution: all degrees of freedom achieve a close balance of excitation and inhibition and become "critical" in the dynamical sense. At long time scales, a complex "breakout" dynamics ensues in which different modes of the system oscillate between prominence and extinction; the model develops various long-tailed statistical behaviors and may become self-organized critical.
PloS one, 2012
Records of excitatory postsynaptic currents (EPSCs) are often complex, with overlapping signals t... more Records of excitatory postsynaptic currents (EPSCs) are often complex, with overlapping signals that display a large range of amplitudes. Statistical analysis of the kinetics and amplitudes of such complex EPSCs is nonetheless essential to the understanding of transmitter release. We therefore developed a maximum-likelihood blind deconvolution algorithm to detect exocytotic events in complex EPSC records. The algorithm is capable of characterizing the kinetics of the prototypical EPSC as well as delineating individual release events at higher temporal resolution than other extant methods. The approach also accommodates data with low signal-to-noise ratios and those with substantial overlaps between events. We demonstrated the algorithm's efficacy on paired whole-cell electrode recordings and synthetic data of high complexity. Using the algorithm to align EPSCs, we characterized their kinetics in a parameter-free way. Combining this approach with maximum-entropy deconvolution, we...
Genome biology, 2002
High-density oligonucleotide arrays (HDONAs) are a powerful tool for assessing differential mRNA ... more High-density oligonucleotide arrays (HDONAs) are a powerful tool for assessing differential mRNA expression levels. To establish the statistical significance of an observed change in expression, one must take into account the noise introduced by the enzymatic and hybridization steps, called type I noise. We undertake an empirical characterization of the experimental repeatability of results by carrying out statistical analysis of a large number of duplicate HDONA experiments. We assign scoring functions for expression ratios and associated quality measures. Both the perfect-match (PM) probes and the differentials between PM and single-mismatch (MM) probes are considered as raw intensities. We then calculate the log-ratio of the noise structure using robust estimates of their intensity-dependent variance. The noise structure in the log-ratios follows a local log-normal distribution in both the PM and PM-MM cases. Significance relative to the type I noise can therefore be quantified r...
Genome biology, 2002
High-density oligonucleotide microarrays provide a powerful tool for assessing differential mRNA ... more High-density oligonucleotide microarrays provide a powerful tool for assessing differential mRNA expression levels. Characterizing the noise resulting from the enzymatic and hybridization steps, called type I noise, is essential for attributing significance measures to the differential expression scores. We introduce scoring functions for expression ratios, and associated quality measures. Both the PM (Perfect Match) probes and PM-MM differentials (MM is the single MisMatch) are considered as raw intensities. We then characterize the log-ratio noise structure using robust estimates of their intensity dependent variance. We show the relationships between the obtained ratios and their quality measures. The complementarity of PM and PM-MM methods is emphasized by the probe sets signal to noise measures. Using a large set of replicate experiments, we demonstrate that the noise structure in the log-ratios very closely follows a local log-normal distribution for both the PM and PM-MM case...
Physical review. E, Statistical, nonlinear, and soft matter physics, 2001
The enzymes that pass DNA through DNA so as to remove entanglements, adenosine-triphosphate-hydro... more The enzymes that pass DNA through DNA so as to remove entanglements, adenosine-triphosphate-hydrolyzing type-II topoisomerases, are able to suppress the probability of self-entanglements (knots) and mutual entanglements (links) between approximately 10 kb plasmids, well below the levels expected, given the assumption that the topoisomerases pass DNA segments at random by thermal motion. This implies that a 10-nm type-II topoisomerase can somehow sense the topology of a large DNA. We previously introduced a "kinetic proofreading" model which supposes the enzyme to require two successive collisions in order to allow exchange of DNA segments, and we showed how it could quantitatively explain the reduction in knotting and linking complexity. Here we show how the same model quantitatively explains the reduced variance of the double-helix linking number (supercoiling) distribution observed experimentally.
Physical review. E, Statistical physics, plasmas, fluids, and related interdisciplinary topics, 2000
We describe a form of memory exhibited by extended excitable systems driven by stochastic fluctua... more We describe a form of memory exhibited by extended excitable systems driven by stochastic fluctuations. Under such conditions, the system self-organizes into a state characterized by power-law correlations, thus retaining long-term memory of previous states. The exponents are robust and model independent. We discuss implications of these results for the functioning of cortical neurons as well as for networks of neurons.
Nature, Jan 28, 1999
Cells must remove all entanglements between their replicated chromosomal DNAs to segregate them d... more Cells must remove all entanglements between their replicated chromosomal DNAs to segregate them during cell division. Entanglement removal is done by ATP-driven enzymes that pass DNA strands through one another, called type II topoisomerases. In vitro, some type II topoisomerases can reduce entanglements much more than expected, given the assumption that they pass DNA segments through one another in a random way. These type II topoisomerases (of less than 10 nm in diameter) thus use ATP hydrolysis to sense and remove entanglements spread along flexible DNA strands of up to 3,000 nm long. Here we propose a mechanism for this, based on the higher rate of collisions along entangled DNA strands, relative to collision rates on disentangled DNA strands. We show theoretically that if a type II topoisomerase requires an initial 'activating' collision before a second strand-passing collision, the probability of entanglement may be reduced to experimentally observed levels. This propo...
Physical review. E, Statistical physics, plasmas, fluids, and related interdisciplinary topics, 1994
Physical review. E, Statistical physics, plasmas, fluids, and related interdisciplinary topics, 1995
Physical review. E, Statistical physics, plasmas, fluids, and related interdisciplinary topics, 1993
Genome research, 2003
Although mRNA decay rates are a key determinant of the steady-state concentration for any given m... more Although mRNA decay rates are a key determinant of the steady-state concentration for any given mRNA species, relatively little is known, on a population level, about what factors influence turnover rates and how these rates are integrated into cellular decisions. We decided to measure mRNA decay rates in two human cell lines with high-density oligonucleotide arrays that enable the measurement of decay rates simultaneously for thousands of mRNA species. Using existing annotation and the Gene Ontology hierarchy of biological processes, we assign mRNAs to functional classes at various levels of resolution and compare the decay rate statistics between these classes. The results show statistically significant organizational principles in the variation of decay rates among functional classes. In particular, transcription factor mRNAs have increased average decay rates compared with other transcripts and are enriched in "fast-decaying" mRNAs with half-lives <2 h. In contrast,...
Physics Letters A, 1996
In biological evolution, the rate of mutations is "encoded" by enzymes which can be mutated like ... more In biological evolution, the rate of mutations is "encoded" by enzymes which can be mutated like any other gene. Inspired by this feature, we present a simple Brownian motion model, in which the temperature itself is a dynamical variable. Intrawell and interwell relaxations occur at different "temperatures" and have different dynamics, and the Kramers time becomes asymptotically linear in the barrier height for large heights.
BACKGROUND: The distribution of chromatin-associated proteins plays a key role in directing nucle... more BACKGROUND: The distribution of chromatin-associated proteins plays a key role in directing nuclear function. Previously, we developed an image-based method to quantify the nuclear distributions of proteins and showed that these distributions depended on the phenotype of human mammary epithelial cells. Here we describe a method that creates a hierarchical tree of the given cell phenotypes and calculates the statistical significance between them, based on the clustering analysis of nuclear protein distributions. RESULTS ...