Structure and extent of DNA methylation-based epigenetic variation in wild emmer wheat (T. turgidum ssp. dicoccoides) populations.

BACKGROUND: The genetic structure and differentiation of wild emmer wheat suggests that genetic diversity is eco-geographically structured. However, very little is known about the structure and extent of the heritable epigenetic variation and its influence on local adaptation in natural populations. RESULTS: The structure and extent of the heritable methylation-based epigenetic variation were assessed within and among natural populations of Triticum turgidum ssp. dicoccoides. We used methylation sensitive amplified polymorphism (MSAP) and transposon methylation display (TMD) techniques, to assess the methylation status of random genomic CCGG sites and CCGG sites flanking transposable elements (TEs), respectively. Both techniques were applied to the DNA of 50 emmer accessions which were collected from five different geographically isolated regions. In order to ensure the assessment of heritable epigenetic variation, all accessions were grown under common garden conditions for two generations. In all accessions, the difference in methylation levels of CCGG sites, including CCGG sites that flanked TEs, were not statistically significant and relatively high, ranging between 46 and 76 %. The pattern of methylation was significantly different among accessions, such that clear and statistically significant population-specific methylation patterns were observed. CONCLUSION: In this study, we have observed population-unique heritable methylation patterns in emmer wheat accessions originating from five geographically isolated regions. Our data indicate that methylation-based epigenetic diversity might be eco-geographically structured and might be partly determined by climatic and edaphic factors.

Discovery of tumoricidal DNA oligonucleotides by response-directed in vitro evolution.

Drug discovery is challenged by ineffectiveness of drugs against variable and evolving diseases, and adverse effects due to poor selectivity. We describe a robust platform which potentially addresses these limitations. The platform enables rapid discovery of DNA oligonucleotides evolved in vitro for exerting specific and selective biological responses in target cells. The process operates without a priori target knowledge (mutations, biomarkers, etc). We report the discovery of oligonucleotides with direct, selective cytotoxicity towards cell lines, as well as patient-derived solid and hematological tumors. A specific oligonucleotide termed E8, induced selective apoptosis in triple-negative breast cancer (TNBC) cells. Polyethylene glycol-modified E8 exhibited favorable biodistribution in animals, persisting in tumors up to 48-hours after injection. E8 inhibited tumors by 50% within 10 days of treatment in patient-derived xenograft mice, and was effective in ex vivo organ cultures from chemotherapy-resistant TNBC patients. These findings highlight a drug discovery model which is target-tailored and on-demand.

Simulating the Monty Hall problem in a DNA sequencing machine.

The Monty Hall problem is a decision problem with an answer that is surprisingly counter-intuitive yet provably correct. Here we simulate and prove this decision in a high-throughput DNA sequencing machine, using a simple encoding. All possible scenarios are represented by DNA oligonucleotides, and gameplay decisions are implemented by sequencing these oligonucleotides from specific positions, with a single run simulating more than 12,000,000 independent games. This work highlights high-throughput DNA sequencing as a new tool that could extend existing capabilities and enable new encoding schemes for problems in DNA computing.