Recent Progress Toward the Templated Synthesis and Directed Evolution of Sequence-Defined Synthetic Polymers

Biological polymers such as nucleic acids and proteins are ubiquitous in living systems, but their ability to address problems beyond those found in nature is constrained by factors such as chemical or biological instability, limited building-block functionality, bioavailability, and immunogenicity. In principle, sequence-defined synthetic polymers based on nonbiological monomers and backbones might overcome these constraints; however, identifying the sequence of a synthetic polymer that possesses a specific desired functional property remains a major challenge. Molecular evolution can rapidly generate functional polymers but requires a means of translating amplifiable templates such as nucleic acids into the polymer being evolved. This review covers recent advances in the enzymatic and nonenzymatic templated polymerization of nonnatural polymers and their potential applications in the directed evolution of sequence-defined synthetic polymers.Chemistry and Chemical Biolog

Effective complexity of stationary process realizations

The concept of effective complexity of an object as the minimal description length of its regularities has been initiated by Gell-Mann and Lloyd. The regularities are modeled by means of ensembles, that is probability distributions on finite binary strings. In our previous paper we propose a definition of effective complexity in precise terms of algorithmic information theory. Here we investigate the effective complexity of binary strings generated by stationary, in general not computable, processes. We show that under not too strong conditions long typical process realizations are effectively simple. Our results become most transparent in the context of coarse effective complexity which is a modification of the original notion of effective complexity that uses less parameters in its definition. A similar modification of the related concept of sophistication has been suggested by Antunes and Fortnow.Comment: 14 pages, no figure

A "metric" complexity for weakly chaotic systems

We consider the number of Bowen sets which are necessary to cover a large measure subset of the phase space. This introduce some complexity indicator characterizing different kind of (weakly) chaotic dynamics. Since in many systems its value is given by a sort of local entropy, this indicator is quite simple to be calculated. We give some example of calculation in nontrivial systems (interval exchanges, piecewise isometries e.g.) and a formula similar to the Ruelle-Pesin one, relating the complexity indicator to some initial condition sensitivity indicators playing the role of positive Lyapunov exponents.Comment: 15 pages, no figures. Articl

Space-Time Complexity in Hamiltonian Dynamics

New notions of the complexity function C(epsilon;t,s) and entropy function S(epsilon;t,s) are introduced to describe systems with nonzero or zero Lyapunov exponents or systems that exhibit strong intermittent behavior with ``flights'', trappings, weak mixing, etc. The important part of the new notions is the first appearance of epsilon-separation of initially close trajectories. The complexity function is similar to the propagator p(t0,x0;t,x) with a replacement of x by the natural lengths s of trajectories, and its introduction does not assume of the space-time independence in the process of evolution of the system. A special stress is done on the choice of variables and the replacement t by eta=ln(t), s by xi=ln(s) makes it possible to consider time-algebraic and space-algebraic complexity and some mixed cases. It is shown that for typical cases the entropy function S(epsilon;xi,eta) possesses invariants (alpha,beta) that describe the fractal dimensions of the space-time structures of trajectories. The invariants (alpha,beta) can be linked to the transport properties of the system, from one side, and to the Riemann invariants for simple waves, from the other side. This analog provides a new meaning for the transport exponent mu that can be considered as the speed of a Riemann wave in the log-phase space of the log-space-time variables. Some other applications of new notions are considered and numerical examples are presented.Comment: 27 pages, 6 figure

Fast and sensitive multiple alignment of large genomic sequences.

BACKGROUND: Genomic sequence alignment is a powerful method for genome analysis and annotation, as alignments are routinely used to identify functional sites such as genes or regulatory elements. With a growing number of partially or completely sequenced genomes, multiple alignment is playing an increasingly important role in these studies. In recent years, various tools for pair-wise and multiple genomic alignment have been proposed. Some of them are extremely fast, but often efficiency is achieved at the expense of sensitivity. One way of combining speed and sensitivity is to use an anchored-alignment approach. In a first step, a fast search program identifies a chain of strong local sequence similarities. In a second step, regions between these anchor points are aligned using a slower but more accurate method. RESULTS: Herein, we present CHAOS, a novel algorithm for rapid identification of chains of local pair-wise sequence similarities. Local alignments calculated by CHAOS are used as anchor points to improve the running time of DIALIGN, a slow but sensitive multiple-alignment tool. We show that this way, the running time of DIALIGN can be reduced by more than 95% for BAC-sized and longer sequences, without affecting the quality of the resulting alignments. We apply our approach to a set of five genomic sequences around the stem-cell-leukemia (SCL) gene and demonstrate that exons and small regulatory elements can be identified by our multiple-alignment procedure. CONCLUSION: We conclude that the novel CHAOS local alignment tool is an effective way to significantly speed up global alignment tools such as DIALIGN without reducing the alignment quality. We likewise demonstrate that the DIALIGN/CHAOS combination is able to accurately align short regulatory sequences in distant orthologues.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Multiple whole genome alignments and novel biomedical applications at the VISTA portal

The VISTA portal for comparative genomics is designed to give biomedical scientists a unified set of tools to lead them from the raw DNA sequences through the alignment and annotation to the visualization of the results. The VISTA portal also hosts the alignments of a number of genomes computed by our group, allowing users to study the regions of their interest without having to manually download the individual sequences. Here we describe various algorithmic and functional improvements implemented in the VISTA portal over the last 2 years. The VISTA Portal is accessible at http://genome.lbl.gov/vista

VARiD: A variation detection framework for color-space and letter-space platforms

Motivation: High-throughput sequencing (HTS) technologies are transforming the study of genomic variation. The various HTS technologies have different sequencing biases and error rates, and while most HTS technologies sequence the residues of the genome directly, generating base calls for each position, the Applied Biosystem's SOLiD platform generates dibase-coded (color space) sequences. While combining data from the various platforms should increase the accuracy of variation detection, to date there are only a few tools that can identify variants from color space data, and none that can analyze color space and regular (letter space) data together