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

This paper presents two sets of techniques for comparing unrooted evolutionary trees, namely, label compression and four-way dvnamic programming. The technique of four-way dynamic programming transforms existing algorithms for computing rooted maximum agree ment subtrees into new ones for unrooted trees. Let n be the size of the two input trees. This technique leads to an O(n log n)-time algorithm for unrooted trees whose degrees are bounded by a constant, matching the best known complexity for the rooted binary case. The technique of label compression is not based on dynamic programming. With this technique, we obtain an O(nl”5 log n)-time algorithm for unrooted trees with arbitrary degrees, also matching the best algorithm for the rooted unbounded degree case.

General techniques for comparing unrooted evolutionary trees

We give a greedy learning algorithm for reconstructing an evolutionary tree based on a harmonic average on triplets of taxa. This algorithm runs in polynomial time in the input size. Using the Jukes-Cantor model of evolution, our algorithm is mathematically proven to require sample sequences of only polynomial lengths in the number of taxa in order to recover the correct tree topology with high probability. In addition to recovering the topology, the algorithm also estimates the tree edge lengths with high accuracy. Our theoretical analysis is supported by simulated experiments, in which the algorithm has demonstrated high success rates, in reconstructing a large tree from short sequences.

Recovering evolutionary trees through harmonic greedy triplets

We study on-line strategies for solving problems with hybrid algorithms. There is a problem Q and w basic algorithms for solving Q. For some � ≤ w, we have a computer withdisjoint memory areas, each of which can be used to run a basic algorithm and store its intermediate results. In the worst case, only one basic algorithm can solve Q in finite time, and all the other basic algorithms run forever without solving Q. To solve Q with a hybrid algorithm constructed from the basic algorithms, we run a basic algorithm for some time, then switch to another, and continue this process until Q is solved. The goal is to solve Q in the least amount of time. Using competitive ratios to measure the efficiency of a hybrid algorithm, we construct an optimal deterministic hybrid algorithm and an efficient randomized hybrid algorithm. This resolves an open question on searching with multiple robots posed by Baeza-Yates, Culberson and Rawlins. We also prove that our randomized algorithm is optimal for � = 1, settling a conjecture of Kao, Reif and Tate.

Optimal constructions of hybrid algorithms

Finding strongly connected components is a fundamental step in many algorithms for directed graphs. In sequential computation this problem has an optimal linear-time algorithm. In parallel computation, however, it remains an open problem whether polylogarithmic time and a linear number of processors are sufficient for computing the strongly connected components on a parallel random-access machine. This paper provides the first nontrivial partial solution to the open problem: for a planar directed graph of size n the strongly connected components can be computed deterministically in $O(\log ^3 n)$ time with ${n / {\log n}}$ processors. The algorithm runs on a parallel random-access machine that allows concurrent reads and concurrent writes in its shared memory and, in case of a write conflict, permits an arbitrary processor to succeed.

Linear-processor NC algorithms for planar directed graphs I: strongly connected components

We give a greedy learning algorithm for reconstructing an evolutionary tree based on a certain harmonic average on triplets of terminal taxa. After the pairwise distances between terminal taxa are estimated from sequence data, the algorithm runs in O(n^2) time using O(n) work space, where n is the number of terminal taxa. These time and space complexities are optimal in the sense that the size of an input distance matrix is n^2 and the size of an output tree is n. Moreover, in the Jukes-Cantor model of evolution, the algorithm recovers the correct tree topology with high probability using sample sequences of length polynomial in (1) n, (2) the logarithm of the error probability, and (3) the inverses of two small parameters.

Ming-Yang Kao

Papers

General techniques for comparing unrooted evolutionary trees

Recovering evolutionary trees through harmonic greedy triplets

Optimal constructions of hybrid algorithms

Linear-processor NC algorithms for planar directed graphs I: strongly connected components

Provably Fast and Accurate Recovery of Evolutionary Trees through Harmonic Greedy Triplets