抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

The emergence of order in natural systems is a constant source of inspiration for both physical and biological sciences. While the spatial order characterizing for example the crystals has been the basis of many advances in contemporary physics, most complex systems in nature do not offer such high degree of order. Many of these systems form complex networks whose nodes are the elements of the system and edges represent the interactions between them. 
Traditionally complex networks have been described by the random graph theory founded in 1959 by Paul Erdohs and Alfred Renyi. One of the defining features of random graphs is that they are statistically homogeneous, and their degree distribution (characterizing the spread in the number of edges starting from a node) is a Poisson distribution. In contrast, recent empirical studies, including the work of our group, indicate that the topology of real networks is much richer than that of random graphs. In particular, the degree distribution of real networks is a power-law, indicating a heterogeneous topology in which the majority of the nodes have a small degree, but there is a significant fraction of highly connected nodes that play an important role in the connectivity of the network. 
The scale-free topology of real networks has very important consequences on their functioning. For example, we have discovered that scale-free networks are extremely resilient to the random disruption of their nodes. On the other hand, the selective removal of the nodes with highest degree induces a rapid breakdown of the network to isolated subparts that cannot communicate with each other. 
The non-trivial scaling of the degree distribution of real networks is also an indication of their assembly and evolution. Indeed, our modeling studies have shown us that there are general principles governing the evolution of networks. Most networks start from a small seed and grow by the addition of new nodes which attach to the nodes already in the system. This process obeys preferential attachment: the new nodes are more likely to connect to nodes with already high degree. We have proposed a simple model based on these two principles wich was able to reproduce the power-law degree distribution of real networks. Perhaps even more importantly, this model paved the way to a new paradigm of network modeling, trying to capture the evolution of networks, not just their static topology.

/pdf/statistical-mechanics-of-complex-networks-1zfjpvxipu.pdf

Statistical mechanics of complex networks

Inspired by empirical studies of networked systems such as the Internet, social networks, and biological networks, researchers have in recent years developed a variety of techniques and models to help us understand or predict the behavior of these systems. Here we review developments in this field, including such concepts as the small-world effect, degree distributions, clustering, network correlations, random graph models, models of network growth and preferential attachment, and dynamical processes taking place on networks.

/pdf/the-structure-and-function-of-complex-networks-34deompc9l.pdf

The Structure and Function of Complex Networks

http://www.maths.qmul.ac.uk/%7Elatora/report_06.pdf

Complex networks: Structure and dynamics

We will review some of the major results in random graphs and some of the more challenging open problems. We will cover algorithmic and structural questions. We will touch on newer models, including those related to the WWW.

Random graphs

......... Non-deterministic polynomial time (commonly termed ‘NP-complete’) problems are relevant to many computational tasks of practical interest—such as the ‘travelling salesman problem’—but are difficult to solve: the computing time grows exponentially with problem size in the worst case. It has recently been shown that these problems exhibit ‘phase boundaries’, across which dramatic changes occur in the computational difficulty and solution character—the problems become easier to solve away from the boundary. Here we report an analytic solution and experimental investigation of the phase transition in K-satisfiability, an archetypal NP-complete problem. Depending on the input parameters, the computing time may grow exponentially or polynomially with problem size; in the former case, we observe a discontinuous transition, whereas in the latter case a continuous (second-order) transition is found. The nature of these transitions may explain the differing computational costs, and suggests directions for improving the efficiency of search algorithms. Similar types of transition should occur in other combinatorial problems and in glassy or granular materials, thereby strengthening the link between computational models and properties of physical systems. Many computational tasks of practical interest are surprisingly difficult to solve even using the fastest available machines. Such problems, found for example in planning, scheduling, machine learning, hardware design, and computational biology, generally belong to the class of NP-complete problems 1‐3 . NP stands for ‘nondeterministic polynomial time’, which denotes an abstract computational model with a rather technical definition. Intuitively speaking, this class of computational tasks consists of problems for which a potential solution can be checked efficiently for correctness, yet finding such a solution appears to require exponential time in the worst case. A good analogy can be drawn from mathematics: proving open conjectures in mathematics is extremely difficult, but verifying any given proof (or solution) is generally relatively straightforward. The class of NP-complete problems lies at the foundations of the theory of computational complexity in modern computer science. Literally thousands of computational problems have been shown to be NP-complete. The completeness property of NPcomplete problems means that if an efficient algorithm for solving just one of these problems could be found, one would immediately have an efficient algorithm for all NP-complete problems. However,

/pdf/determining-computational-complexity-from-characteristic-1ym67n4k1j.pdf

Determining computational complexity from characteristic 'phase transitions.'

The metastable states of a glass are localized and counted by adding a weak pinning field that explicitly breaks the ergodicity. The entropy of the metastable states, that is, the logarithm of their number, is extensive in a range of temperatures ${T}_{s}lTl{T}_{c}$ only. It is argued that ${T}_{s}$ and ${T}_{c}$ are the ideal calorimetric and kinetic transition temperatures, respectively. An explicit computation of the metastable states entropy for a $({\stackrel{\ensuremath{\rightarrow}}{\ensuremath{\varphi}}}^{2}{)}^{2}$ model is given.

Structural glass transition and the entropy of the metastable states.

Complexity of neural systems often makes impracticable explicit measurements of all interactions between their constituents. Inverse statistical physics approaches, which infer effective couplings between neurons from their spiking activity, have been so far hindered by their computational complexity. Here, we present 2 complementary, computationally efficient inverse algorithms based on the Ising and “leaky integrate-and-fire” models. We apply those algorithms to reanalyze multielectrode recordings in the salamander retina in darkness and under random visual stimulus. We find strong positive couplings between nearby ganglion cells common to both stimuli, whereas long-range couplings appear under random stimulus only. The uncertainty on the inferred couplings due to limitations in the recordings (duration, small area covered on the retina) is discussed. Our methods will allow real-time evaluation of couplings for large assemblies of neurons.

http://nba.uth.tmc.edu/homepage/cnjclub/2009Fall/cocco2009a.pdf

Neuronal couplings between retinal ganglion cells inferred by efficient inverse statistical physics methods.

The spectral properties of the Laplacian operator on “small-world” lattices, that is mixtures of unidimensional chains and random graphs structures are investigated numerically and analytically. A transfer matrix formalism including a self-consistent potential a la Edwards is introduced. In the extended region of the spectrum, an effective medium calculation provides the density of states and pseudo relations of dispersion for the eigenmodes in close agreement with the simulations. Localization effects, which are due to connectivity fluctuations of the sites are shown to be quantitatively described by the single defect approximation recently introduced for random graphs.

/pdf/diffusion-localization-and-dispersion-relations-on-small-9seb6moc37.pdf

Diffusion, localization and dispersion relations on "small-world" lattices

In the course of evolution, proteins undergo important changes in their amino acid sequences, while their three-dimensional folded structure and their biological function remain remarkably conserved. Thanks to modern sequencing techniques, sequence data accumulate at unprecedented pace. This provides large sets of so-called homologous, i.e. evolutionarily related protein sequences, to which methods of inverse statistical physics can be applied. Using sequence data as the basis for the inference of Boltzmann distributions from samples of microscopic configurations or observables, it is possible to extract information about evolutionary constraints and thus protein function and structure. Here we give an overview over some biologically important questions, and how statistical-mechanics inspired modeling approaches can help to answer them. Finally, we discuss some open questions, which we expect to be addressed over the next years.

https://iopscience.iop.org/article/10.1088/1361-6633/aa9965/pdf

Rémi Monasson

Papers

Determining computational complexity from characteristic 'phase transitions.'

Structural glass transition and the entropy of the metastable states.

Neuronal couplings between retinal ganglion cells inferred by efficient inverse statistical physics methods.

Diffusion, localization and dispersion relations on "small-world" lattices

Inverse statistical physics of protein sequences: a key issues review.