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

Studies statistical database problems for 2D tables whose regular cells, row sums, column sums and table sums may be suppressed. Using graph-theoretical techniques, we give optimal or efficient algorithms for the query system problem, the adversary problem and the minimum complementary suppression problem. These three problems are considered for a variety of data security requirements such as those of protecting linear invariants, analytic invariants, k rows (or columns) as a whole, and a table as a whole.

Security problems for statistical databases with general cell suppressions

We propose a mathematical model of DNA self-assembly using 2D tiles to form 3D nanostructures. This is the first work to combine studies in self-assembly and nanotechnology in 3D, just as Rothemund and Winfree did in the 2D case. Our model is a more precise superset of their Tile Assembly Model that facilitates building scalable 3D molecules. Under our model, we present algorithms to build a hollow cube, which is intuitively one of the simplest 3D structures to construct. We also introduce five basic measures of complexity to analyze these algorithms. Our model and algorithmic techniques are applicable to more complex 2D and 3D nanostructures.

DNA Self-Assembly For Constructing 3D Boxes

We present a new technique called balanced randomized tree splitting. It is useful in constructing unknown trees recursively. By applying it we obtain two new results on efficient construction of evolutionary trees: a new upper time-bound on the problem of constructing an evolutionary tree from experiments, and a relatively fast approximation algorithm for the maximum agreement subtree problem for binary trees for which the maximum number of leaves in an optimal solution is large. We also present new lower bounds for the problem of constructing an evolutionary tree from experiments and for the problem of constructing a tree from an ultrametric distance matrix.

Balanced randomized tree splitting with applications to evolutionary tree constructions

Patterned self-assembly tile set synthesis (PATS) aims at finding a minimum tile set to uniquely self-assemble a given rectangular (color) pattern. For k >= 1, k-PATS is a variant of PATS that restricts input patterns to those with at most $k$ colors. A computer-assisted proof has been recently proposed for 2-PATS by Kari et al. [arXiv:1404.0967 (2014)]. In contrast, the best known manually-checkable proof is for the NP-hardness of 29-PATS by Johnsen, Kao, and Seki [ISAAC 2013, LNCS 8283, pp.~699-710]. We propose a manually-checkable proof for the NP-hardness of 11-PATS.

A manually-checkable proof for the NP-hardness of 11-color pattern self-assembly tile set synthesis

This short note reports a master theorem on tight asymptotic solutions to divide-and-conquer recurrences with more than one recursive term: for example, T(n) = 1/4 T(n/16) + 1/3 T(3n/5) + 4 T(n/100) + 10 T(n/300) + n^2.

Ming-Yang Kao

Papers

Security problems for statistical databases with general cell suppressions

DNA Self-Assembly For Constructing 3D Boxes

Balanced randomized tree splitting with applications to evolutionary tree constructions

A manually-checkable proof for the NP-hardness of 11-color pattern self-assembly tile set synthesis

Multiple-size divide-and-conquer recurrences