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Bilbao, A.

Publications and source records attributed to Bilbao, A..

7 recordsLinked to original sources

The Everything Bagel Feature Finder: Ultra-fast automated feature finding for untargeted metabolomics

Metabolomics studies are increasingly being applied with hundreds to thousands, even tens of thousands of samples that demand rapid, automated data processing while maintaining analytical sensitivity or quantitative accuracy. A major computational bottleneck is feature finding, which is the transformation of LC-MS and LC-MS/MS data into a set of analyte signals aligned and quantified across samples. Feature finding can be computationally intensive and often requires manual iterative parameter optimization. To accelerate this process, we present the Everything Bagel (EB) feature finder, an ultra-fast automated feature finding tool that integrates feature detection, retention-time alignment, and gap filling designed for run-time and memory efficiency. We benchmarked EB against two automated feature finding methods on eight benchmarking datasets. Specifically, we evaluated these three feature finding methods by measuring spike-in standard detection coverage, dilution series quantification accuracy, and yeast 12C/13C credentialed features. In this evaluation, the EB feature finder achieved performance comparable to, and often exceeding, existing methods while requiring up to 150-fold lower CPU hours and up to 113-fold lower wall time. We further demonstrated the bioanalytical validity of EB by reanalyzing published datasets used for biomarker discovery and reproduced biologically significant features that matched the published findings using manually tuned feature finding settings. Taken along with the speed improvements, we anticipate EB will enhance the ability to automatically analyze datasets with thousands to tens of thousands of samples for the community.

bioinformatics↗

Data Independent Acquisition Pipeline for Microbiome Samples (Microbe-DIA)

The functional complexity inherent in microbiomes complicates analytical approaches aimed at defining phenotype. As proteins are the functional effectors of microbiome phenotypes, improving the performance of mass spectrometry-based metaproteomics is critical to achieving the functional characterization of these systems. Data-independent acquisition (DIA) improves protein coverage and reduces data missingness when compared to data-dependent acquisition (DDA) in metaproteomics. However, the application of DIA to complex microbial systems remains constrained by analytical throughput and computational scalability. Here, we optimized LC-MS/MS acquisition parameters for both DDA and DIA using a model microbiome, demonstrating how DIA enables increased sample throughput without compromising quantitative performance. In addition, we demonstrated a computationally efficient, library-free DIA workflow that overcomes reliance on empirical spectral libraries. Our analytical and computational innovations establish a scalable and cost-effective pipeline for metaproteomics of complex microbial communities.

microbiology↗

An LLM-driven pipeline for proteomics-based detection and structural modeling of post-translational modifications

Post-translational modifications (PTMs) on proteins dynamically regulate their functions and subsequently cellular physiology. Significant advances have been made in their detection and modeling: mass spectrometry-based proteomics has become the cornerstone for PTM detection in complex samples, while emerging structure-prediction frameworks enable modeling of PTM-dependent conformational changes. However, the biological significance of many PTMs remains largely unexplored, in part because integrated pipelines that bridge PTM detection with structural modeling remain limited. We present a generative AI-driven pipeline that integrates PTM detection with structural modeling of their effects on protein dynamics and interactions. The pipeline comprises two complementary tools: PTMdiscoverer and PTM-Psi. First, PTMdiscoverer leverages large language models to identify, annotate, and interpret candidate PTMs from open-search proteomics results, addressing limitations of conventional proteomics tools. Next, PTM-Psi models the structural, functional, and dynamic consequences of these spatially aware modifications on protein dynamics. These two components bridge PTM discovery with mechanistic interpretation at the structural level. We demonstrate our pipeline by using cyanobacterial proteomics data to study potential molecular mechanisms of redox-regulated "dark complex" formation in carbon metabolism, advancing our ability to interpret PTM-mediated regulation in microbial systems.

bioinformatics↗

Introducing Molecular Hypernetworks forDiscovery in MultidimensionalMetabolomics Data

Orthogonal separations of data from high-resolution mass spectrometry can provide insight into sample composition and help address the challenge of complete annotation of molecules in untargeted metabolomics. "Molecular networks" (MNs), as used, for example, in the Global Natural Products Social Molecular Networking platform, are an increasingly popular computational strategy for exploring and visualizing molecular relationships and improving annotation. MNs use graph representations to show the re-lationships between measured multidimensional data features. MNs also show promise for using network science algorithms to automatically identify targets for annotation candidates and to dereplicate features associated to a single molecular identity. How-ever, more advanced methods may better represent the complexity present in samples. Our work aims to increase confidence in annotation propagation by extending molecular network methods to include "molecular hypernetworks" (MHNs), able to natively repre-sent multiway relationships among observations supporting both human and analytical processing. In this paper we first introduce MHNs illustrated with simple examples, and demonstrate how to build them from liquid chromatography-and ion mobility spectrometry-separated MS data. We then describe a method to construct MHNs di-rectly from existing MNs as their "clique reconstructions", demonstrating their utility by comparing examples of previously published graph-based MNs to their respective MHNs.

bioinformatics↗

Metabolomic, photoprotective, and photosynthetic acclimatory responses to post-flowering drought in sorghum

Climate change is globally affecting rainfall patterns, necessitating the improvement of drought tolerance in crops. Sorghum bicolor is a drought-tolerant cereal capable of producing high yields under water scarcity conditions. Functional stay-green sorghum genotypes can maintain green leaf area and efficient grain filling in terminal post-flowering water deprivation, a period of ~10 weeks. To obtain molecular insights into these characteristics, two drought-tolerant genotypes, BTx642 and RTx430, were grown in control and terminal post-flowering drought field plots in the Central Valley of California. Photosynthetic, photoprotective, water dynamics, and biomass traits were quantified and correlated with metabolomic data collected from leaves, stems, and roots at multiple timepoints during drought. Physiological and metabolomic data was then compared to longitudinal RNA sequencing data collected from these two genotypes. The metabolic response to drought highlights the uniqueness of the post-flowering drought acclimation relative to pre-flowering drought. The functional stay-green genotype BTx642 specifically induced photoprotective responses in post-flowering drought supporting a putative role for photoprotection in the molecular basis of the functional stay-green trait. Specific genes are highlighted that may contribute to post-flowering drought tolerance and that can be targeted in crops to maximize yields under limited water input conditions. HighlightPathways contributing to the long-term maintenance of photosynthetic activity in terminal post-flowering drought are revealed by a comprehensive approach combining in-field photosynthetic physiological analysis, metabolomics, and transcriptomics.

plant biology↗

Female mice are more prone to develop an addictive-like phenotype for sugar consumption

BackgroundThe concept of "sugar addiction" is gaining increasing attention in both the lay media and scientific literature. However, the concept of sugar addiction is controversial and only a few studies have attempted to determine the "addictive" properties of sugar using rigorous scientific criteria. ObjectiveHere we set out to systematically test the addictive properties of sugar in male and female mice using established paradigms and models from the drug addiction field. MethodsMale and female C57BL/6N (8-10 weeks old) were evaluated in 4 experimental procedures to study the addictive properties of sugar: (i) a drinking in the dark (DID) procedure to model sugar binging; (ii) a long-term free choice home cage drinking procedure measuring the sugar deprivation effect (SDE) following an abstinence phase; (iii) a long-term operant sugar self-administration with persistence, motivation and compulsivity measures and (iv) intracranial self-administration (ICSS). ResultsFemale mice were more vulnerable to the addictive properties of sugar than male mice, showing higher binge and long-term, excessive drinking, a more pronounced relapse-like drinking following deprivation, and higher persistence and motivation for sugar. No sex differences were seen in a compulsivity test or reward sensitivity measured using ICSS following extended sugar consumption. ConclusionThis study demonstrates the occurrence of an addictive-like phenotype for sugar in male and female mice, similar to drugs of abuse, and suggests sex-dependent differences in the development of sugar addiction.

neuroscience↗

Single-dose ethanol intoxication causes acute and lasting neuronal changes in the brain

Alcohol intoxication at early ages is a risk factor for development of addictive behavior. To uncover neuronal molecular correlates of acute ethanol intoxication, we used stable-isotope labeled mice combined with quantitative mass spectrometry to screen over 2000 hippocampal proteins of which 72 changed synaptic abundance up to two-fold after ethanol exposure. Among those were mitochondrial proteins and proteins important for neuronal morphology, including MAP6 and Ankyrin-G. Based on these candidate proteins, we found acute and lasting molecular, cellular, and behavioral changes following a single intoxication in alcohol-naive mice. Immunofluorescence analysis revealed a shortening of axon initial segments. Longitudinal two-photon in vivo imaging showed increased synaptic dynamics and mitochondrial trafficking in axons. Knockdown of mitochondrial trafficking in dopaminergic neurons abolished conditioned alcohol preference in Drosophila. This introduces mitochondrial trafficking as a process implicated in reward learning, and highlights the potential of high-resolution proteomics to identify cellular mechanisms relevant for addictive behavior.

neuroscience↗