Evolution of Protein Molecules

THE JOURNAL OF BIOLOGICAL CHEMISTRY: The Biochemical Behavior of LeadL I. Influence of Calcium, Phosphorus, and Vitamin D on Lead in Blood and Bone

To construct sophisticated biochemical circuits from scratch, one needs to understand how simple the building blocks can be and how robustly such circuits can scale up. Using a simple DNA reaction mechanism based on a reversible strand displacement process, we experimentally demonstrated several digital logic circuits, culminating in a four-bit square-root circuit that comprises 130 DNA strands. These multilayer circuits include thresholding and catalysis within every logical operation to perform digital signal restoration, which enables fast and reliable function in large circuits with roughly constant switching time and linear signal propagation delays. The design naturally incorporates other crucial elements for large-scale circuitry, such as general debugging tools, parallel circuit preparation, and an abstraction hierarchy supported by an automated circuit compiler.

http://science.sciencemag.org/content/sci/332/6034/1196.full.pdf

Scaling Up Digital Circuit Computation with DNA Strand Displacement Cascades

A number of different approaches have been described to identify proteins from tandem mass spectrometry (MS/MS) data. The most common approaches rely on the available databases to match experimental MS/MS data. These methods suffer from several drawbacks and cannot be used for the identification of proteins from unknown genomes. In this communication, we describe a new de novo sequencing software package, PEAKS, to extract amino acid sequence information without the use of databases. PEAKS uses a new model and a new algorithm to efficiently compute the best peptide sequences whose fragment ions can best interpret the peaks in the MS/MS spectrum. The output of the software gives amino acid sequences with confidence scores for the entire sequences, as well as an additional novel positional scoring scheme for portions of the sequences. The performance of PEAKS is compared with Lutefisk, a well-known de novo sequencing software, using quadrupole-time-of-flight (Q-TOF) data obtained for several tryptic peptides from standard proteins.

/pdf/peaks-powerful-software-for-peptide-de-novo-sequencing-by-1htzy7q8mi.pdf

PEAKS: powerful software for peptide de novo sequencing by tandem mass spectrometry

The impressive capabilities of the mammalian brain—ranging from perception, pattern recognition and memory formation to decision making and motor activity control—have inspired their re-creation in a wide range of artificial intelligence systems for applications such as face recognition, anomaly detection, medical diagnosis and robotic vehicle control Yet before neuron-based brains evolved, complex biomolecular circuits provided individual cells with the ‘intelligent’ behaviour required for survival However, the study of how molecules can ‘think’ has not produced an equal variety of computational models and applications of artificial chemical systems Although biomolecular systems have been hypothesized to carry out neural-network-like computations in vivo and the synthesis of artificial chemical analogues has been proposed theoretically, experimental work has so far fallen short of fully implementing even a single neuron Here, building on the richness of DNA computing and strand displacement circuitry, we show how molecular systems can exhibit autonomous brain-like behaviours Using a simple DNA gate architecture that allows experimental scale-up of multilayer digital circuits, we systematically transform arbitrary linear threshold circuits (an artificial neural network model) into DNA strand displacement cascades that function as small neural networks Our approach even allows us to implement a Hopfield associative memory with four fully connected artificial neurons that, after training in silico, remembers four single-stranded DNA patterns and recalls the most similar one when presented with an incomplete pattern Our results suggest that DNA strand displacement cascades could be used to endow autonomous chemical systems with the capability of recognizing patterns of molecular events, making decisions and responding to the environment

/pdf/neural-network-computation-with-dna-strand-displacement-2m7egtgffn.pdf

Neural network computation with DNA strand displacement cascades

The family of Vickrey-Clarke-Groves (VCG) mechanisms is arguably the most celebrated achievement in truthful mechanism design. However, VCG mechanisms have their limitations. They only apply to optimization problems with a utilitarian (or affine) objective function, and their output should optimize the objective function. For many optimization problems, finding the optimal output is computationally intractable. If we apply VCG mechanisms to polynomial-time algorithms that approximate the optimal solution, the resulting mechanisms may no longer be truthful.In light of these limitations, it is useful to study whether we can design a truthful non-VCG payment scheme that is computationally tractable for a given allocation rule O. In this paper, we focus our attention on emphbinary demand games in which the agents' only available actions are to take part in the a game or not to. For these problems, we prove that a truthful mechanism M=(O, P) exists with a proper payment method P iff the allocation rule O satisfies a certain monotonicity property. We provide a general framework to design such P. We further propose several general composition-based techniques to compute P efficiently for various types of output. In particular, we show how P can be computed through "or/and" combinations, round-based combinations, and some more complex combinations of the outputs from subgames.

/pdf/towards-truthful-mechanisms-for-binary-demand-games-a-3277jvuj1z.pdf

Towards truthful mechanisms for binary demand games: a general framework

We extend the classic on-line search problem known as the cow-path problem to the case in which goal locations are selected according to one of a set of possible known probability distributions. We present a polynomial-time linear-programming algorithm for this problem.

/pdf/algorithms-for-informed-cows-58illyb71h.pdf

Algorithms for Informed Cows

Background
In recent years, quartet-based phylogeny reconstruction methods have received considerable attentions in the computational biology community. Traditionally, the accuracy of a phylogeny reconstruction method is measured by simulations on synthetic datasets with known "true" phylogenies, while little theoretical analysis has been done. In this paper, we present a new model-based approach to measuring the accuracy of a quartet-based phylogeny reconstruction method. Under this model, we propose three efficient algorithms to reconstruct the "true" phylogeny with a high success probability.

/pdf/reconstructing-phylogenies-from-noisy-quartets-in-polynomial-2q3jsrarrv.pdf

Reconstructing phylogenies from noisy quartets in polynomial time with a high success probability

In this paper, a linear-time algorithm, which is optimal, is presented to solve the haplotype inference problem for pedigree data when there are no recombinations and the pedigree has no mating loops. The approach is based on the use of graphs to capture SNP, Mendelian and parity constraints of the given pedigree.

Linear-Time haplotype inference on pedigrees without recombinations

We propose a fast methodology for encoding graphs with information-theoretically minimum numbers of bits. Specifically, a graph with property pi is called a pi-graph. If pi satisfies certain properties, then an n-node m-edge pi-graph G can be encoded by a binary string X such that (1) G and X can be obtained from each other in O(n log n) time, and (2) X has at most beta(n)+o(beta(n)) bits for any continuous super-additive function beta(n) so that there are at most 2^{beta(n)+o(beta(n))} distinct n-node pi-graphs. The methodology is applicable to general classes of graphs; this paper focuses on planar graphs. Examples of such pi include all conjunctions over the following groups of properties: (1) G is a planar graph or a plane graph; (2) G is directed or undirected; (3) G is triangulated, triconnected, biconnected, merely connected, or not required to be connected; (4) the nodes of G are labeled with labels from {1, ..., ell_1} for ell_1 <= n; (5) the edges of G are labeled with labels from {1, ..., ell_2} for ell_2 <= m; and (6) each node (respectively, edge) of G has at most ell_3 = O(1) self-loops (respectively, ell_4 = O(1) multiple edges). Moreover, ell_3 and ell_4 are not required to be O(1) for the cases of pi being a plane triangulation. These examples are novel applications of small cycle separators of planar graphs and are the only nontrivial classes of graphs, other than rooted trees, with known polynomial-time information-theoretically optimal coding schemes.

Ming-Yang Kao

Papers

Towards truthful mechanisms for binary demand games: a general framework

Algorithms for Informed Cows

Reconstructing phylogenies from noisy quartets in polynomial time with a high success probability

Linear-Time haplotype inference on pedigrees without recombinations

A Fast General Methodology for Information-Theoretically Optimal Encodings of Graphs