Probabilistic reasoning with a bayesian DNA device based on strand displacement

We present a computing model based on the DNA strand displacement technique which performs Bayesian inference. The model will take single stranded DNA as input data, representing the presence or absence of a specific molecular signal (evidence). The program logic encodes the prior probability of a disease and the conditional probability of a signal given the disease playing with a set of different DNA complexes and their ratios. When the input and program molecules interact, they release a different pair of single stranded DNA species whose relative proportion represents the application of Bayes? Law: the conditional probability of the disease given the signal. The models presented in this paper can empower the application of probabilistic reasoning in genetic diagnosis in vitro

An auxin-regulable oscillatory circuit drives the root clock in Arabidopsis

CSIC - Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA)In Arabidopsis, the root clock regulates the spacing of lateral organs along the primary root through oscillating gene expression. The core molecular mechanism that drives the root clock periodicity and how it is modified by exogenous cues such as auxin and gravity remain unknown. We identified the key elements of the oscillator (AUXIN RESPONSE FACTOR 7, its auxin-sensitive inhibitor IAA18/POTENT, and auxin) that form a negative regulatory loop circuit in the oscillation zone. Through multilevel computer modeling fitted to experimental data, we explain how gene expression oscillations coordinate with cell division and growth to create the periodic pattern of organ spacing. Furthermore, gravistimulation experiments based on the model predictions show that external auxin stimuli can lead to entrainment of the root clock. Our work demonstrates the mechanism underlying a robust biological clock and how it can respond to external stimuli.This work was funded by the Ministerio de Economía y Competitividad of Spain (MINECO) and/or the ERDF (BFU2016-80315-P to M.A.M.-R., BIO2017-82209-R to J.C.d.P., and TIN2016-81079-R to A.R.-P.), the Comunidad de Madrid and/or ERDF and ESF (2017-T1/BIO-5654 to K.W. and S2017/BMD-3691 to A.R.-P.), the Howard Hughes Medical Institute and the NIH (R35-GM131725 to P.N.B.), the Fonds Wetenschappelijk Onderzoek (FWO Flanders) (G022516N, G020918N, and G024118N to T.B.), and the “Severo Ochoa Program for Centres of Excellence in R&D” from the Agencia Estatal de Investigacion of Spain [SEV-2016-0672 (2017–2021)] to K.W., P.P.-G., and M.A.M.-R. through CBGP. M.M. was supported by a postdoctoral contract associated to SEV-2016-0672, E.B.-A. by Ayudante de Investigacion contract PEJ-2017-AI/BIO-7360 from the Comunidad de Madrid, A.S.-C. and L.S.-R. by FPI contracts from MINECO (BES-2014-068852 and BES-2017-080155, respectively), J.C. by a Juan de la Cierva contract from MINECO (FJCI-2016-28607), P.P.-G. by a Juan de la Cierva contract from MINECO (FJCI-2015-24905) and Programa Atraccion Talento from Comunidad Madrid (2017-T2/BIO-3453), A.S. by a Torres Quevedo contract from MINECO (PTQ-15-07915), and K.W. by program PGC2018-093387-A-I00 from the Ministerio de Ciencia e Innovacion (MICIU)Peer reviewe

Context measure in qualitative reasoning

This paper deals with a classical Artificial Intelligence problem, knowledge representation, though from an original and new angle, based on uncertainty processing, Information Theory and systems complexity, which provide a generic and fitting framework upon which to establish the validity and completeness requirements and quality criteria to be satisfied by all the representations. The objectives are clear - prevent errors occurring when formalizing knowledge and come as close as possible to reality -; however, the methods and techniques to do so are not. The adaptation of the representation to the information provided by the expert and the adaptation of the information represented to the system user environment are the two basic questions addressed by this study, which introduces concepts such as dissonance, confusion, nonspecificity and complexity

Nanoinformatics and DNA-based computing: catalyzing nanomedicine

Five decades of research and practical application of computers in biomedicine has given rise to the discipline of medical informatics, which has made many advances in genomic and translational medicine possible. Developments in nanotechnology are opening up the prospects for nanomedicine and regenerative medicine where informatics and DNA computing can become the catalysts enabling health care applications at sub-molecular or atomic scales. Although nanomedicine promises a new exciting frontier for clinical practice and biomedical research, issues involving cost-effectiveness studies, clinical trials and toxicity assays, drug delivery methods, and the implementation of new personalized therapies still remain challenging. Nanoinformatics can accelerate the introduction of nano-related research and applications into clinical practice, leading to an area that could be called “translational nanoinformatics.” At the same time, DNA and RNA computing presents an entirely novel paradigm for computation. Nanoinformatics and DNA-based computing are together likely to completely change the way we model and process information in biomedicine and impact the emerging field of nanomedicine most strongly. In this article, we review work in nanoinformatics and DNA (and RNA)-based computing, including applications in nanopediatrics. We analyze their scientific foundations, current research and projects, envisioned applications and potential problems that might arise from them

Comparación de dos estrategias de vacunación frente a la hepatitis A y B en individuos con hepatitis crónica C Comparison of two vaccination strategies against hepatitis A and B in patients with chronic hepatitis C

Objetivo: aunque se recomienda vacunar frente al virus de la hepatitis A (VHA) y al virus de la hepatitis B (VHB) a los pacientes con infección crónica por el virus de la hepatitis C (VHC), la estrategia de vacunación más costo-efectiva aún no está establecida. Nuestro objetivo fue comparar la vacunación universal (de todos los individuos) con la selectiva (únicamente de los individuos no inmunizados) frente al VHA y al VHB de los pacientes con infección crónica por VHC en nuestro medio. Pacientes y métodos: comparamos los costes directos de las dos estrategias de vacunación frente a ambos virus en 313 individuos con infección crónica por VHC. Determinamos los marcadores serológicos del VHA (anti-VHA) y del VHB (HBsAg, anti-HBs y anti-HBc) y tuvimos en cuenta los costes de vacunas y reactivos en nuestro ámbito. Resultados: la prevalencia de anti-VHA fue del 81,2% y la de anti-HBc del 24,6%. La prevalencia de anti-VHA aumentaba progresivamente con la edad. La inmunización frente al VHA suponía 19.806,64 € con la estrategia universal y 9.899,62 € con la selectiva. La vacunación frente al VHB ascendía a 18.780 € con la inmunización universal y a 20.385,57 € con la selectiva (mediante el anti-HBc). Se analizaron los costes considerando distintos grupos etarios y diversos factores de riesgo. Conclusiones: en nuestros individuos con infección crónica por VHC la vacunación selectiva frente al VHA es la más costoefectiva. Pero cuando el porcentaje de inmunización frente al VHA desciende por debajo del 20% la mejor opción es la universal. La diferencia en la costoefectividad de ambas estrategias de vacunación frente al VHB es pequeña, a favor de la universal, por lo que en subgrupos con elevada prevalencia de anti-HBc, como adictos a drogas y tatuados, la selectiva podría ser la mejor alternativa.Objective: although the vaccination against hepatitis A (VAH) and hepatitis B (VBH) is recommended in patients with HCV, the most cost-effective strategy has not been established. Our objective was to compare the cost-effectiveness of universal strategy (vaccination all patients) with selective strategy (vaccination only patients against virus they lack immunity to) in patients with HCV. Patients and methods: we compared the direct medical costs of the two vaccination strategies against both viruses in 313 patients with HC. Serological markers for HAV (anti-HAV) and HBV (HbsAg, anti HBs, anti HBc) were determined in the 313 patients and the costs of the vaccines and the blood tests necessary to determinate the immunity state in our care system were considered. Results: the prevalence of anti-HAV was 81,2% and of anti-HBc was 24,6%. The prevalence of anti-HAV increases with age. HAV vaccination with universal strategy has a cost of 19.806,64 € and with selective one of 9.899,62 €. HBV vaccination with universal strategy rose to 18.780 € and to 20.385,57 € with selective one (employing anti-HBc). Costs were analysed in different groups of age and several hepatitis HBV risk factors. Conclusions: the selective vaccination strategy against HAV was most cost-effective in our patients with HCV. However, when the prevalence of the anti-HAV decreased to less than 20% universal strategy will be the best option. Difference of cost-effective between the two vaccination strategies against HBV was small, on behalf of universal one, so in groups with higher anti-HBc prevalence, like parenteral drugs users and tattoos, the selective strategy could be the best option