Compiler-aided systematic construction of large-scale DNA strand displacement circuits using unpurified components

Biochemical circuits made of rationally designed DNA molecules are proofs of concept for embedding control within complex molecular environments. They hold promise for transforming the current technologies in chemistry, biology, medicine and material science by introducing programmable and responsive behaviour to diverse molecular systems. As the transformative power of a technology depends on its accessibility, two main challenges are an automated design process and simple experimental procedures. Here we demonstrate the use of circuit design software, combined with the use of unpurified strands and simplified experimental procedures, for creating a complex DNA strand displacement circuit that consists of 78 distinct species. We develop a systematic procedure for overcoming the challenges involved in using unpurified DNA strands. We also develop a model that takes synthesis errors into consideration and semi-quantitatively reproduces the experimental data. Our methods now enable even novice researchers to successfully design and construct complex DNA strand displacement circuits

Leaderless deterministic chemical reaction networks

This paper answers an open question of Chen, Doty, and Soloveichik [1], who showed that a function f:N^k --> N^l is deterministically computable by a stochastic chemical reaction network (CRN) if and only if the graph of f is a semilinear subset of N^{k+l}. That construction crucially used "leaders": the ability to start in an initial configuration with constant but non-zero counts of species other than the k species X_1,...,X_k representing the input to the function f. The authors asked whether deterministic CRNs without a leader retain the same power. We answer this question affirmatively, showing that every semilinear function is deterministically computable by a CRN whose initial configuration contains only the input species X_1,...,X_k, and zero counts of every other species. We show that this CRN completes in expected time O(n), where n is the total number of input molecules. This time bound is slower than the O(log^5 n) achieved in [1], but faster than the O(n log n) achieved by the direct construction of [1] (Theorem 4.1 in the latest online version of [1]), since the fast construction of that paper (Theorem 4.4) relied heavily on the use of a fast, error-prone CRN that computes arbitrary computable functions, and which crucially uses a leader.Comment: arXiv admin note: substantial text overlap with arXiv:1204.417

Compiler-aided systematic construction of large-scale DNA strand displacement circuits using unpurified components

Biochemical circuits made of rationally designed DNA molecules are proofs of concept for embedding control within complex molecular environments. They hold promise for transforming the current technologies in chemistry, biology, medicine and material science by introducing programmable and responsive behaviour to diverse molecular systems. As the transformative power of a technology depends on its accessibility, two main challenges are an automated design process and simple experimental procedures. Here we demonstrate the use of circuit design software, combined with the use of unpurified strands and simplified experimental procedures, for creating a complex DNA strand displacement circuit that consists of 78 distinct species. We develop a systematic procedure for overcoming the challenges involved in using unpurified DNA strands. We also develop a model that takes synthesis errors into consideration and semi-quantitatively reproduces the experimental data. Our methods now enable even novice researchers to successfully design and construct complex DNA strand displacement circuits

High harmonic generation and periodic level crossings

Published versio

Creation and Validation of the Spanish Durum Wheat Core Collection.

Spanish wheat (Triticum spp.) landraces have a considerable polymorphism, containing many unique alleles, relative to other collections. The existence of a core collection is a favored approach for breeders to efficiently explore novel variation and enhance the use of germplasm. In this study, the Spanish durum wheat (Triticum turgidum L.) core collection (CC) was created using a population structure–based method, grouping accessions by subspecies and allocating the number of genotypes among populations according to the diversity of simple sequence repeat (SSR) markers. The CC of 94 genotypes was established, which accounted for 17% of the accessions in the entire collection. An alternative core collection (CH), with the same number of genotypes per subspecies and maximizing the coverage of SSR alleles, was assembled with the Core Hunter software. The quality of both core collections was compared with a random core collection and evaluated using geographic, agromorphological, and molecular marker data not previously used in the selection of genotypes. Both core collections had a high genetic representativeness, which validated their sampling strategies. Geographic and agromorphological variation, phenotypic correlations, and gliadin alleles of the original collection were more accurately depicted by the CC. Diversity arrays technology (DArT) markers revealed that the CC included genotypes less similar than the CH. Although more SSR alleles were retained by the CH (94%) than by the CC (91%), the results showed that the CC was better than CH for breeding purposes

Determination of genetic structure of germplasm collections: are traditional hierarchical clustering methods appropriate for molecular marker data?

Despite the availability of newer approaches, traditional hierarchical clustering remains very popular in genetic diversity studies in plants. However, little is known about its suitability for molecular marker data. We studied the performance of traditional hierarchical clustering techniques using real and simulated molecular marker data. Our study also compared the performance of traditional hierarchical clustering with model-based clustering (STRUCTURE). We showed that the cophenetic correlation coefficient is directly related to subgroup differentiation and can thus be used as an indicator of the presence of genetically distinct subgroups in germplasm collections. Whereas UPGMA performed well in preserving distances between accessions, Ward excelled in recovering groups. Our results also showed a close similarity between clusters obtained by Ward and by STRUCTURE. Traditional cluster analysis can provide an easy and effective way of determining structure in germplasm collections using molecular marker data, and, the output can be used for sampling core collections or for association studies

SWiM: Secure Wildcard Pattern Matching From OT Extension

Suppose a server holds a long text string and a receiver holds a short pattern string. Secure pattern matching allows the receiver to learn the locations in the long text where the pattern appears, while leaking nothing else to either party besides the length of their inputs. In this work we consider secure wildcard pattern matching WPM, where the receiver\u27s pattern is allowed to contain wildcards that match to any character. We present SWiM, a simple and fast protocol for WPM that is heavily based on oblivious transfer (OT) extension. As such, the protocol requires only a small constant number of public-key operations and otherwise uses only very fast symmetric-key primitives. SWiM is secure against semi-honest adversaries. We implemented a prototype of our protocol to demonstrate its practicality. We can perform WPM on a DNA text (4-character alphabet) of length $10^5$ and pattern of length $10^3$ in just over 2 seconds, which is over two orders of magnitude faster than the state-of-the-art scheme of Baron et al. (SCN 2012)