Information transmission in genetic regulatory networks: a review

These are notes for a set of 7 two-hour lectures given at the 2010 Summer School on Quantitative Evolutionary and Comparative Genomics at OIST, Okinawa, Japan. The emphasis is on understanding how biological systems process information. We take a physicist's approach of looking for simple phenomenological descriptions that can address the questions of biological function without necessarily modeling all (mostly unknown) microscopic details; the example that is developed throu...

In computer science, we can theoretically neatly separate transmission and processing of information, hardware and software, and programs and their inputs. This is much more intricate in biology, Nevertheless, I argue that Shannon's concept of information is useful in biology, although its application is not as straightforward as many people think. In fact, the recently developed theory of information decomposition can shed much light on the complementarity between coding and...

In the postgenome era many efforts have been dedicated to systematically elucidate the complex web of interacting genes and proteins. These efforts include experimental and computational methods. Microarray technology offers an opportunity for monitoring gene expression level at the genome scale. By recourse to information theory, this study proposes a mathematical approach to reconstruct gene regulatory networks at coarse-grain level from high throughput gene expression data...

We quantify the influence of the topology of a transcriptional regulatory network on its ability to process environmental signals. By posing the problem in terms of information theory, we may do this without specifying the function performed by the network. Specifically, we study the maximum mutual information between the input (chemical) signal and the output (genetic) response attainable by the network in the context of an analytic model of particle number fluctuations. We ...

In order to survive, reproduce and (in multicellular organisms) differentiate, cells must control the concentrations of the myriad different proteins that are encoded in the genome. The precision of this control is limited by the inevitable randomness of individual molecular events. Here we explore how cells can maximize their control power in the presence of these physical limits; formally, we solve the theoretical problem of maximizing the information transferred from input...

The growth rate of organisms depends both on external conditions and on internal states, such as the expression levels of various genes. We show that to achieve a criterion mean growth rate over an ensemble of conditions, the internal variables must carry a minimum number of bits of information about those conditions. Evolutionary competition thus can select for cellular mechanisms that are more efficient in an abstract, information theoretic sense. Estimates based on recent ...

Changes in a cell's external or internal conditions are usually reflected in the concentrations of the relevant transcription factors. These proteins in turn modulate the expression levels of the genes under their control and sometimes need to perform non-trivial computations that integrate several inputs and affect multiple genes. At the same time, the activities of the regulated genes would fluctuate even if the inputs were held fixed, as a consequence of the intrinsic nois...

Life depends as much on the flow of information as on the flow of energy. Here we review the many efforts to make this intuition precise. Starting with the building blocks of information theory, we explore examples where it has been possible to measure, directly, the flow of information in biological networks, or more generally where information theoretic ideas have been used to guide the analysis of experiments. Systems of interest range from single molecules (the sequence d...

We define the concept of dependence among multiple variables using maximum entropy techniques and introduce a graphical notation to denote the dependencies. Direct inference of information theoretic quantities from data uncovers dependencies even in undersampled regimes when the joint probability distribution cannot be reliably estimated. The method is tested on synthetic data. We anticipate it to be useful for inference of genetic circuits and other biological signaling netw...

Living cells are continually exposed to environmental signals that vary in time. These signals are detected and processed by biochemical networks, which are often highly stochastic. To understand how cells cope with a fluctuating environment, we therefore have to understand how reliably biochemical networks can transmit time-varying signals. To this end, we must understand both the noise characteristics and the amplification properties of networks. In this manuscript, we use ...