@lpachter Your cup of tea over at UCLA next week? Regulatory & Epigenetic Stochasticity in Development & Disease http://www.ipam.ucla.edu/programs/workshops/regulatory-and-epigenetic-stochasticity-in-development-and-disease
Category: Microbiology
👓 A Conversation with @LPachter (BS ’94) | Caltech
Pachter, a computational biologist, returns to CalTech to study the role and function of RNA.
🔖 The Epidemic Spreading Model and the Direction of Information Flow in Brain Networks
The interplay between structural connections and emerging information flow in the human brain remains an open research problem. A recent study observed global patterns of directional information flow in empirical data using the measure of transfer entropy. For higher frequency bands, the overall direction of information flow was from posterior to anterior regions whereas an anterior-to-posterior pattern was observed in lower frequency bands. In this study, we applied a simple Susceptible-Infected-Susceptible (SIS) epidemic spreading model on the human connectome with the aim to reveal the topological properties of the structural network that give rise to these global patterns. We found that direct structural connections induced higher transfer entropy between two brain regions and that transfer entropy decreased with increasing distance between nodes (in terms of hops in the structural network). Applying the SIS model, we were able to confirm the empirically observed opposite information flow patterns and posterior hubs in the structural network seem to play a dominant role in the network dynamics. For small time scales, when these hubs acted as strong receivers of information, the global pattern of information flow was in the posterior-to-anterior direction and in the opposite direction when they were strong senders. Our analysis suggests that these global patterns of directional information flow are the result of an unequal spatial distribution of the structural degree between posterior and anterior regions and their directions seem to be linked to different time scales of the spreading process.
IPAM Workshop on Regulatory and Epigenetic Stochasticity in Development and Disease, March 1-3
Epigenetics refers to information transmitted during cell division other than the DNA sequence per se, and it is the language that distinguishes stem cells from somatic cells, one organ from another, and even identical twins from each other. In contrast to the DNA sequence, the epigenome is relatively susceptible to modification by the environment as well as stochastic perturbations over time, adding to phenotypic diversity in the population. Despite its strong ties to the environment, epigenetics has never been well reconciled to evolutionary thinking, and in fact there is now strong evidence against the transmission of so-called “epi-alleles,” i.e. epigenetic modifications that pass through the germline.
However, genetic variants that regulate stochastic fluctuation of gene expression and phenotypes in the offspring appear to be transmitted as an epigenetic or even Lamarckian trait. Furthermore, even the normal process of cellular differentiation from a single cell to a complex organism is not understood well from a mathematical point of view. There is increasingly strong evidence that stem cells are highly heterogeneous and in fact stochasticity is necessary for pluripotency. This process appears to be tightly regulated through the epigenome in development. Moreover, in these biological contexts, “stochasticity” is hardly synonymous with “noise”, which often refers to variation which obscures a “true signal” (e.g., measurement error) or which is structural, as in physics (e.g., quantum noise). In contrast, “stochastic regulation” refers to purposeful, programmed variation; the fluctuations are random but there is no true signal to mask.
This workshop will serve as a forum for scientists and engineers with an interest in computational biology to explore the role of stochasticity in regulation, development and evolution, and its epigenetic basis. Just as thinking about stochasticity was transformative in physics and in some areas of biology, it promises to fundamentally transform modern genetics and help to explain phase transitions such as differentiation and cancer.
This workshop will include a poster session; a request for poster titles will be sent to registered participants in advance of the workshop.
Speaker List:
Adam Arkin (Lawrence Berkeley Laboratory)
Gábor Balázsi (SUNY Stony Brook)
Domitilla Del Vecchio (Massachusetts Institute of Technology)
Michael Elowitz (California Institute of Technology)
Andrew Feinberg (Johns Hopkins University)
Don Geman (Johns Hopkins University)
Anita Göndör (Karolinska Institutet)
John Goutsias (Johns Hopkins University)
Garrett Jenkinson (Johns Hopkins University)
Andre Levchenko (Yale University)
Olgica Milenkovic (University of Illinois)
Johan Paulsson (Harvard University)
Leor Weinberger (University of California, San Francisco (UCSF))
Adam Arkin (Lawrence Berkeley Laboratory)
Gábor Balázsi (SUNY Stony Brook)
Domitilla Del Vecchio (Massachusetts Institute of Technology)
Michael Elowitz (California Institute of Technology)
Andrew Feinberg (Johns Hopkins University)
Don Geman (Johns Hopkins University)
Anita Göndör (Karolinska Institutet)
John Goutsias (Johns Hopkins University)
Garrett Jenkinson (Johns Hopkins University)
Andre Levchenko (Yale University)
Olgica Milenkovic (University of Illinois)
Johan Paulsson (Harvard University)
Leor Weinberger (University of California, San Francisco (UCSF))
🔖 Statistical Physics of Adaptation
Whether by virtue of being prepared in a slowly relaxing, high-free energy initial condition, or because they are constantly dissipating energy absorbed from a strong external drive, many systems subject to thermal fluctuations are not expected to behave in the way they would at thermal equilibrium. Rather, the probability of finding such a system in a given microscopic arrangement may deviate strongly from the Boltzmann distribution, raising the question of whether thermodynamics still has anything to tell us about which arrangements are the most likely to be observed. In this work, we build on past results governing nonequilibrium thermodynamics and define a generalized Helmholtz free energy that exactly delineates the various factors that quantitatively contribute to the relative probabilities of different outcomes in far-from-equilibrium stochastic dynamics. By applying this expression to the analysis of two examples—namely, a particle hopping in an oscillating energy landscape and a population composed of two types of exponentially growing self-replicators—we illustrate a simple relationship between outcome-likelihood and dissipative history. In closing, we discuss the possible relevance of such a thermodynamic principle for our understanding of self-organization in complex systems, paying particular attention to a possible analogy to the way evolutionary adaptations emerge in living things.
🔖 Meaning = Information + Evolution by Carlo Rovelli
Notions like meaning, signal, intentionality, are difficult to relate to a physical word. I study a purely physical definition of "meaningful information", from which these notions can be derived. It is inspired by a model recently illustrated by Kolchinsky and Wolpert, and improves on Dretske classic work on the relation between knowledge and information. I discuss what makes a physical process into a "signal".
🔖 Energy flow and the organization of life | Complexity
Understanding the emergence and robustness of life requires accounting for both chemical specificity and statistical generality. We argue that the reverse of a common observation—that life requires a source of free energy to persist—provides an appropriate principle to understand the emergence, organization, and persistence of life on earth. Life, and in particular core biochemistry, has many properties of a relaxation channel that was driven into existence by free energy stresses from the earth's geochemistry. Like lightning or convective storms, the carbon, nitrogen, and phosphorus fluxes through core anabolic pathways make sense as the order parameters in a phase transition from an abiotic to a living state of the geosphere. Interpreting core pathways as order parameters would both explain their stability over billions of years, and perhaps predict the uniqueness of specific optimal chemical pathways.
Download .pdf copy
[1]
H. Morowitz and E. Smith, “Energy flow and the organization of life,” Complexity, vol. 13, no. 1. Wiley-Blackwell, pp. 51–59, 2007 [Online]. Available: http://dx.doi.org/10.1002/cplx.20191
🔖 Evidence for a limit to human lifespan | Nature Research
Driven by technological progress, human life expectancy has increased greatly since the nineteenth century. Demographic evidence has revealed an ongoing reduction in old-age mortality and a rise of the maximum age at death, which may gradually extend human longevity. Together with observations that lifespan in various animal species is flexible and can be increased by genetic or pharmaceutical intervention, these results have led to suggestions that longevity may not be subject to strict, species-specific genetic constraints. Here, by analysing global demographic data, we show that improvements in survival with age tend to decline after age 100, and that the age at death of the world’s oldest person has not increased since the 1990s. Our results strongly suggest that the maximum lifespan of humans is fixed and subject to natural constraints.
[1]
X. Dong, B. Milholland, and J. Vijg, “Evidence for a limit to human lifespan.,” Nature, vol. 538, no. 7624, pp. 257–259, Oct. 2016. [PubMed]
🔖 Hayflick, his limit, and cellular ageing | Nature Reviews Molecular Cell Biology
Almost 40 years ago, Leonard Hayflick discovered that cultured normal human cells have limited capacity to divide, after which they become senescent — a phenomenon now known as the ‘Hayflick limit’. Hayflick's findings were strongly challenged at the time, and continue to be questioned in a few circles, but his achievements have enabled others to make considerable progress towards understanding and manipulating the molecular mechanisms of ageing.
[1]
J. Shay and W. Wright, “Hayflick, his limit, and cellular ageing.,” Nat Rev Mol Cell Biol, vol. 1, no. 1, pp. 72–6, Oct. 2000. [PubMed]
🔖 Thermodynamic Uncertainty Relation for Biomolecular Processes, Phys. Rev. Lett. 114, 158101 (2015)
Biomolecular systems like molecular motors or pumps, transcription and translation machinery, and other enzymatic reactions, can be described as Markov processes on a suitable network. We show quite generally that, in a steady state, the dispersion of observables, like the number of consumed or produced molecules or the number of steps of a motor, is constrained by the thermodynamic cost of generating it. An uncertainty ε requires at least a cost of 2k_B T/ε^2 independent of the time required to generate the output.
[1]
A. C. Barato and U. Seifert, “Thermodynamic Uncertainty Relation for Biomolecular Processes,” Physical Review Letters, vol. 114, no. 15. American Physical Society (APS), 15-Apr-2015 [Online]. Available: http://dx.doi.org/10.1103/PhysRevLett.114.158101 [Source]
🔖 Causal Entropic Forces, Phys. Rev. Lett. 110, 168702 (2013)
Recent advances in fields ranging from cosmology to computer science have hinted at a possible deep connection between intelligence and entropy maximization, but no formal physical relationship between them has yet been established. Here, we explicitly propose a first step toward such a relationship in the form of a causal generalization of entropic forces that we find can cause two defining behaviors of the human “cognitive niche”—tool use and social cooperation—to spontaneously emerge in simple physical systems. Our results suggest a potentially general thermodynamic model of adaptive behavior as a nonequilibrium process in open systems.
[1]
A. D. Wissner-Gross and C. E. Freer, “Causal Entropic Forces,” Physical Review Letters, vol. 110, no. 16. American Physical Society (APS), 19-Apr-2013 [Online]. Available: http://dx.doi.org/10.1103/PhysRevLett.110.168702 [Source]
🔖 How Life (and Death) Spring From Disorder | Quanta Magazine
Life was long thought to obey its own set of rules. But as simple systems show signs of lifelike behavior, scientists are arguing about whether this apparent complexity is all a consequence of thermodynamics.
This is a nice little general interest article by Philip Ball that does a relatively good job of covering several of my favorite topics (information theory, biology, complexity) for the layperson. While it stays relatively basic, it links to a handful of really great references, many of which I’ve already read, though several appear to be new to me. [1][2][3][4][5][6][7][8][9][10]
While Ball has a broad area of interests and coverage in his work, he’s certainly one of the best journalists working in this subarea of interests today. I highly recommend his work to those who find this area interesting.
References
[1]
E. Mayr, What Makes Biology Unique? Cambridge University Press, 2004.
[2]
A. Wissner-Gross and C. Freer, “Causal entropic forces.,” Phys Rev Lett, vol. 110, no. 16, p. 168702, Apr. 2013. [PubMed]
[3]
A. Barato and U. Seifert, “Thermodynamic uncertainty relation for biomolecular processes.,” Phys Rev Lett, vol. 114, no. 15, p. 158101, Apr. 2015. [PubMed]
[4]
J. Shay and W. Wright, “Hayflick, his limit, and cellular ageing.,” Nat Rev Mol Cell Biol, vol. 1, no. 1, pp. 72–6, Oct. 2000. [PubMed]
[5]
X. Dong, B. Milholland, and J. Vijg, “Evidence for a limit to human lifespan,” Nature, vol. 538, no. 7624. Springer Nature, pp. 257–259, 05-Oct-2016 [Online]. Available: http://dx.doi.org/10.1038/nature19793
[6]
H. Morowitz and E. Smith, “Energy Flow and the Organization of Life,” Santa Fe Institute, 07-Aug-2006. [Online]. Available: http://samoa.santafe.edu/media/workingpapers/06-08-029.pdf. [Accessed: 03-Feb-2017]
[7]
R. Landauer, “Irreversibility and Heat Generation in the Computing Process,” IBM Journal of Research and Development, vol. 5, no. 3. IBM, pp. 183–191, Jul-1961 [Online]. Available: http://dx.doi.org/10.1147/rd.53.0183
[8]
C. Rovelli, “Meaning = Information + Evolution,” arXiv, Nov. 2006 [Online]. Available: https://arxiv.org/abs/1611.02420
[9]
N. Perunov, R. A. Marsland, and J. L. England, “Statistical Physics of Adaptation,” Physical Review X, vol. 6, no. 2. American Physical Society (APS), 16-Jun-2016 [Online]. Available: http://dx.doi.org/10.1103/PhysRevX.6.021036 [Source]
[10]
S. Still, D. A. Sivak, A. J. Bell, and G. E. Crooks, “Thermodynamics of Prediction,” Physical Review Letters, vol. 109, no. 12. American Physical Society (APS), 19-Sep-2012 [Online]. Available: http://dx.doi.org/10.1103/PhysRevLett.109.120604 [Source]
How Life Turns Asymmetric | Quanta Magazine
Scientists are uncovering how our bodies — and everything within them — tell right from left.
🎧 The Power Of Categories | Invisibilia (NPR)
The Power Of Categories examines how categories define us — how, if given a chance, humans will jump into one category or another. People need them, want them. The show looks at what categories provide for us, and you'll hear about a person caught between categories in a way that will surprise you. Plus, a trip to a retirement community designed to help seniors revisit a long-missed category.
The transgender/sexual dysphoria story here is exceedingly interesting because it could potentially have some clues to how those pieces of biology work and what shifts things in one direction or another. How is that spectrum created/defined? A few dozen individuals like that could help provide an answer.
The story about the Indian retirement community in Florida is interesting, but it also raises the (unasked, in the episode at least) question of the detriment it can do to a group of people to be lead by some the oldest members of their community. The Latin words senīlis (“of or pertaining to old age”) and senex (“old”) are the roots of words like senate, senescence, senility, senior, and seniority, and though it’s nice to take care of our elders, the younger generations should take a hard look at the unintended consequences which may stem from this.
In some sense I’m also reminded about Thomas Kuhn’s book The Structure of Scientific Revolutions and why progress in science (and yes, society) is held back by the older generations who are still holding onto outdated models. Though simultaneously, they do provide some useful “brakes” on both velocity of change as well as potential ill effects which could be damaging in short timeframes.
NIMBioS Tutorial: Uncertainty Quantification for Biological Models
NIMBioS will host an Tutorial on Uncertainty Quantification for Biological Models
Uncertainty Quantification for Biological Models
Meeting dates: June 26-28, 2017
Location: NIMBioS at the University of Tennessee, Knoxville
Organizers:
Marisa Eisenberg, School of Public Health, Univ. of Michigan
Ben Fitzpatrick, Mathematics, Loyola Marymount Univ.
James Hyman, Mathematics, Tulane Univ.
Ralph Smith, Mathematics, North Carolina State Univ.
Clayton Webster, Computational and Applied Mathematics (CAM), Oak Ridge National Laboratory; Mathematics, Univ. of Tennessee
Objectives:
Mathematical modeling and computer simulations are widely used to predict the behavior of complex biological phenomena. However, increased computational resources have allowed scientists to ask a deeper question, namely, “how do the uncertainties ubiquitous in all modeling efforts affect the output of such predictive simulations?” Examples include both epistemic (lack of knowledge) and aleatoric (intrinsic variability) uncertainties and encompass uncertainty coming from inaccurate physical measurements, bias in mathematical descriptions, as well as errors coming from numerical approximations of computational simulations. Because it is essential for dealing with realistic experimental data and assessing the reliability of predictions based on numerical simulations, research in uncertainty quantification (UQ) ultimately aims to address these challenges.
Uncertainty quantification (UQ) uses quantitative methods to characterize and reduce uncertainties in mathematical models, and techniques from sampling, numerical approximations, and sensitivity analysis can help to apportion the uncertainty from models to different variables. Critical to achieving validated predictive computations, both forward and inverse UQ analysis have become critical modeling components for a wide range of scientific applications. Techniques from these fields are rapidly evolving to keep pace with the increasing emphasis on models that require quantified uncertainties for large-scale applications. This tutorial will focus on the application of these methods and techniques to mathematical models in the life sciences and will provide researchers with the basic concepts, theory, and algorithms necessary to quantify input and response uncertainties and perform sensitivity analysis for simulation models. Concepts to be covered may include: probability and statistics, parameter selection techniques, frequentist and Bayesian model calibration, propagation of uncertainties, quantification of model discrepancy, adaptive surrogate model construction, high-dimensional approximation, random sampling and sparse grids, as well as local and global sensitivity analysis.
This tutorial is intended for graduate students, postdocs and researchers in mathematics, statistics, computer science and biology. A basic knowledge of probability, linear algebra, and differential equations is assumed.
Application deadline: March 1, 2017
To apply, you must complete an application on our online registration system:
- Click here to access the system
- Login or register
- Complete your user profile (if you haven’t already)
- Find this tutorial event under Current Events Open for Application and click on Apply
Participation in NIMBioS tutorials is by application only. Individuals with a strong interest in the topic are encouraged to apply, and successful applicants will be notified within two weeks after the application deadline. If needed, financial support for travel, meals, and lodging is available for tutorial attendees.
Summary Report. TBA
Live Stream. The Tutorial will be streamed live. Note that NIMBioS Tutorials involve open discussion and not necessarily a succession of talks. In addition, the schedule as posted may change during the Workshop. To view the live stream, visit http://www.nimbios.org/videos/livestream. A live chat of the event will take place via Twitter using the hashtag #uncertaintyTT. The Twitter feed will be displayed to the right of the live stream. We encourage you to post questions/comments and engage in discussion with respect to our Social Media Guidelines.
Source: NIMBioS Tutorial: Uncertainty Quantification for Biological Models