Pedro Saa
Especialidad:
Statistical learning, estadística bayesiana, métodos monte carlo, optimización.
Email:
pnsaa@ing.puc.cl
Pedro es profesor asistente del Departamento de Ingeniería Química y Bioprocesos del Instituto de Ingeniería Matemática y Computacional (IMC UC). Con formación en biología computacional y de sistemas, su interés de investigación se centra en la integración de métodos de machine y stastical learning a sistemas biológicos apoyados en modelos físicos.
PUBLICACIONES
lisher: Advances in Information Retrieval Link>
ABSTRACT
Bifidobacterium longum subsp. infantis is a representative and dominant species in the infant gut and is considered a beneficial microbe. This organism displays multiple adaptations to thrive in the infant gut, regarded as a model for human milk oligosaccharides (HMOs) utilization. These carbohydrates are abundant in breast milk and include different molecules based on lactose. They contain fucose, sialic acid, and N-acetylglucosamine. Bifidobacterium metabolism is complex, and a systems view of relevant metabolic pathways and exchange metabolites during HMO consumption is missing. To address this limitation, a refined genome-scale network reconstruction of this bacterium is presented using a previous reconstruction of B. infantis ATCC 15967 as a template. The latter was expanded based on an extensive revision of genome annotations, current literature, and transcriptomic data integration. The metabolic reconstruction (iLR578) accounted for 578 genes, 1,047 reactions, and 924 metabolites. Starting from this reconstruction, we built context-specific genome-scale metabolic models using RNA-seq data from cultures growing in lactose and three HMOs. The models revealed notable differences in HMO metabolism depending on the functional characteristics of the substrates. Particularly, fucosyl-lactose showed a divergent metabolism due to a fucose moiety. High yields of lactate and acetate were predicted under growth rate maximization in all conditions, whereas formate, ethanol, and 1,2-propanediol were substantially lower. Similar results were also obtained under near-optimal growth on each substrate when varying the empirically observed acetate-to-lactate production ratio. Model predictions displayed reasonable agreement between central carbon metabolism fluxes and expression data across all conditions. Flux coupling analysis revealed additional connections between succinate exchange and arginine and sulfate metabolism and a strong coupling between central carbon reactions and adenine metabolism. More importantly, specific networks of coupled reactions under each carbon source were derived and analyzed. Overall, the presented network reconstruction constitutes a valuable platform for probing the metabolism of this prominent infant gut bifidobacteria.
Publisher: BMC Bioinformatics Link>
Background
Uniform random sampling of mass-balanced flux solutions offers an unbiased appraisal of the capabilities of metabolic networks. Unfortunately, it is impossible to avoid thermodynamically infeasible loops in flux samples when using convex samplers on large metabolic models. Current strategies for randomly sampling the non-convex loopless flux space display limited efficiency and lack theoretical guarantees.Results
Here, we present LooplessFluxSampler, an efficient algorithm for exploring the loopless mass-balanced flux solution space of metabolic models, based on an Adaptive Directions Sampling on a Box (ADSB) algorithm. ADSB is rooted in the general Adaptive Direction Sampling (ADS) framework, specifically the Parallel ADS, for which theoretical convergence and irreducibility results are available for sampling from arbitrary distributions. By sampling directions that adapt to the target distribution, ADSB traverses more efficiently the sample space achieving faster mixing than other methods. Importantly, the presented algorithm is guaranteed to target the uniform distribution over convex regions, and it provably converges on the latter distribution over more general (non-convex) regions provided the sample can have full support.Conclusions
LooplessFluxSampler enables scalable statistical inference of the loopless mass-balanced solution space of large metabolic models. Grounded in a theoretically sound framework, this toolbox provides not only efficient but also reliable results for exploring the properties of the almost surely non-convex loopless flux space. Finally, LooplessFluxSampler includes a Markov Chain diagnostics suite for assessing the quality of the final sample and the performance of the algorithm.
Publisher: Iscience, Link>
ABSTRACT
The sudden loss of smell is among the earliest and most prevalent symptoms of COVID-19 when measured with a clinical psychophysical test. Research has shown the potential impact of frequent screening for olfactory dysfunction, but existing tests are expensive and time consuming. We developed a low-cost ($0.50/test) rapid psychophysical olfactory test (KOR) for frequent testing and a model-based COVID-19 screening framework using a Bayes Network symptoms model. We trained and validated the model on two samples: suspected COVID-19 cases in five healthcare centers (n = 926; 33% prevalence, 309 RT-PCR confirmed) and healthy miners (n = 1,365; 1.1% prevalence, 15 RT-PCR confirmed). The model predicted COVID-19 status with 76% and 96% accuracy in the healthcare and miners samples, respectively (healthcare: AUC = 0.79 [0.75–0.82], sensitivity: 59%, specificity: 87%; miners: AUC = 0.71 [0.63–0.79], sensitivity: 40%, specificity: 97%, at 0.50 infection probability threshold). Our results highlight the potential for low-cost, frequent, accessible, routine COVID-19 testing to support society's reopening.
Edificio de Innovación UC, Piso 2
Vicuña Mackenna 4860
Macul, Chile
Vicuña Mackenna 4860
Macul, Chile