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da Silva, R.

Publications and source records attributed to da Silva, R..

8 recordsLinked to original sources

Mitigation of intertidal temperature extremes by algal canopies

In a rapidly warming world, species must either adapt to changing environmental conditions, shift their distributions through the movement and survival of individuals, or face local or global extinction. Within ecosystems, structural complexity of either environmental or biogenic origin may provide microclimate buffering, promoting persistence. In coastal environments, it has long been stated that macroalgae act as important ecosystem engineers that can moderate thermal extremes, however the magnitude of this buffering has rarely been quantified. Moreover, the extent to which thermal buffering varies among macroalgal species, and how it relates to thermal heterogeneity across scales remains poorly understood. Here, we measured thermal buffering provided by intertidal macroalgae using high-frequency, high-spatial-resolution in situ temperature logging. We compared microclimates beneath algal cover with those on experimentally cleared bare rock across two tidal levels, two solar exposures and two seasons along six shores within a biogeographical transition zone. Thermal buffering was highly heterogeneous across the study area, varying with species identity, algal cover, tidal level, and solar exposure. Together, these factors generated a complex thermal mosaic, with even small algal specimens providing measurable buffering. We found that latitude had little influence on mean daytime low-tide temperatures, whereas local-scale factors had pronounced effects. Lower tidal position, reduced solar exposure, and algal cover each moderated thermal conditions and, in combination, provided an average cooling of approximately 4 {degrees}C. These findings highlight the importance of fine-scale habitat heterogeneity in shaping thermal exposure and identify features that could be incorporated into local climate-adaptation strategies, supporting coastal conservation and restoration efforts.

ecology↗

DeepSEA: an alignment-free deep learning tool for functional annotation of antimicrobial resistance proteins

Antimicrobial resistance (AMR) is one of the most concerning modern threats as it places a greater burden on health systems than HIV and malaria combined. Current surveillance strategies for tracking antimicrobial resistance (AMR) rely on genomic comparisons and depend on sequence alignment with strict similarity cutoffs of greater than 95%. Therefore, these methods have high false-negative error rates due to a lack of reference sequences with a representative coverage of AMR protein diversity. Deep learning (DL) has been used as an alternative to sequence alignment, as artificial neural networks (ANNs) can extract abstract features from data and therefore limit the need for sequence comparisons. Here, a convolutional neural network (CNN) was trained to differentiate antimicrobial resistance proteins from nonresistance proteins and functionally annotate them in nine resistance classes. Our model demonstrated higher recall values (>0.9) than the alignment-based approach for all protein classes tested. Additionally, our CNN architecture allowed us to investigate internal states and explain the model classification regarding protein domain feature importance related to antimicrobial molecule inactivation. Finally, we built an open-source bioinformatic tool that can be used to annotate antimicrobial resistance proteins and provide information on protein domains without sequence alignment.

bioinformatics↗

The feature landscape of visual cortex

Understanding computations in the visual system requires a characterization of the distinct feature preferences of neurons in different visual cortical areas. However, we know little about how feature preferences of neurons within a given area relate to that areas role within the global organization of visual cortex. To address this, we recorded from thousands of neurons across six visual cortical areas in mouse and leveraged generative AI methods combined with closed-loop neuronal recordings to identify each neurons visual feature preference. First, we discovered that the mouses visual system is globally organized to encode features in a manner invariant to the types of image transformations induced by self-motion. Second, we found differences in the visual feature preferences of each area and that these differences generalized across animals. Finally, we observed that a given areas collection of preferred stimuli ( own-stimuli) drive neurons from the same area more effectively through their dynamic range compared to preferred stimuli from other areas ( other-stimuli). As a result, feature preferences of neurons within an area are organized to maximally encode differences among own-stimuli while remaining insensitive to differences among other-stimuli. These results reveal how visual areas work together to efficiently encode information about the external world.

neuroscience↗

A supervised fingerprint-based strategy to connect natural product mass spectrometry fragmentation data to their biosynthetic gene clusters

Microbial specialized metabolites are an important source of and inspiration for many pharmaceutical, biotechnological products and play key roles in ecological processes. However, most bioactivity-guided isolation and identification methods widely employed in metabolite discovery programs do not explore the full biosynthetic potential of an organism. Untargeted metabolomics using liquid chromatography coupled with tandem mass spectrometry is an efficient technique to access metabolites from fractions and even environmental crude extracts. Nevertheless, metabolomics is limited in predicting structures or bioactivities for cryptic metabolites. Linking the biosynthetic potential inferred from (meta)genomics to the specialized metabolome would accelerate drug discovery programs. Here, we present a k-nearest neighbor classifier to systematically connect mass spectrometry fragmentation spectra to their corresponding biosynthetic gene clusters (independent of their chemical compound class). Our pipeline offers an efficient method to link biosynthetic genes to known, analogous, or cryptic metabolites that they encode for, as detected via mass spectrometry from bacterial cultures or environmental microbiomes. Using paired data sets that include validated genes-mass spectral links from the Paired Omics Data Platform, we demonstrate this approach by automatically linking 18 previously known mass spectra to their corresponding previously experimentally validated biosynthetic genes (i.e., via NMR or genetic engineering). Finally, we demonstrated that this new approach is a substantial step towards making in silico (and even de novo) structure predictions for peptidic metabolites and a glycosylated terpene. Altogether, we conclude that NPOmix minimizes the need for culturing and facilitates specialized metabolite isolation and structure elucidation based on integrative omics mining. SignificanceThe pace of natural product discovery has remained relatively constant over the last two decades. At the same time, there is an urgent need to find new therapeutics to fight antibiotic-resistant bacteria, cancer, tropical parasites, pathogenic viruses, and other severe diseases. Here, we introduce a new machine learning algorithm that can efficiently connect metabolites to their biosynthetic genes. Our Natural Products Mixed Omics (NPOmix) tool provides access to genomic information for bioactivity, class, (partial) structure, and stereochemistry predictions to prioritize relevant metabolite products and facilitate their structural elucidation. Our approach can be applied to biosynthetic genes from bacteria (used in this study), fungi, algae, and plants where (meta)genomes are paired with corresponding mass fragmentation data.

bioinformatics↗

What's left in the tank? Identification of non-ascribed aquarium's coral collections with DNA barcodes as part of an integrated diagnostic approach

The unprecedented threats to coral reef ecosystems from global climate change (GCC) require an urgent response from the aquarium community, which is becoming an increasingly vital coral conservation resource. Unfortunately, many hermatypic corals in aquaria are not identified to species level, which hinders assessment of their conservation significance. Traditional methods of species identification using morphology can be challenging, especially to non-taxonomists. DNA barcoding is an option for species identification of Scleractinian corals, especially when used in concert with morphology-based assessment. This study uses DNA barcodes to try to identify aquarium specimens of the diverse reef-forming genus Acropora from 127 samples. We identified to our best current knowledge, to species name 44% of the analysed samples and provided provisional identification for 80% of them (101/127, in the form of a list of species names with associate confidence values). We highlighted a sampling bias in public nucleotide sequences repertories (e.g.: GenBank) towards more charismatic and more studied species, even inside a well-studied genus like Acropora. In addition, we showed a potential "single observer" effect with over a quarter of the reference sequences used for these identifications coming from the same study. We propose the use of barcoding and query matching as an additional tool for taxonomic experts and general aquarists, as an additional tool to increase their chances of making high confidence species-level identifications. We produce a standardised and easily repeatable methodology to increase the capacity of aquariums and other facilities to assess non-ascribed species, emphasising the value of integrating this approach with morphological identification optimising usage of authoritative identification guides and expert opinion.

genetics↗

The Molecular and Microbial Microenvironments in Chronically Diseased Lungs

To visualize the personalized distributions of pathogens, chemical environments including microbial metabolites, pharmaceuticals, and their metabolic products within and between human lungs afflicted with cystic fibrosis, we generated 3D microbiome and metabolome maps of six explanted lungs from three cystic fibrosis patients. These 3D spatial maps revealed that the chemical environments are variable between patients and within the lungs of each patient. Although the patients microbial ecosystems were defined by the dominant pathogen, their chemical diversity was not. Additionally, the chemical diversity between locales in lungs of the same individual sometimes exceeded inter-individual variation. Thus, the chemistry and microbiome of the explanted lungs appear to be not only personalized but also regiospecific. Previously undescribed analogs of microbial quinolones and antibiotic metabolites were also detected. Furthermore, mapping the chemical and microbial distributions allowed visualization of microbial community interactions, such as increased production of quorum sensing quinolones in locations where Pseudomonas was in contact with Staphylococcus and Granulicatella, consistent with in vitro observations of bacteria isolated from these patients. Visualization of microbe-metabolite associations within a host organ in early-stage CF disease in animal models will help elucidate a complex interplay between the presence of a given microbial structure, antibiotics, metabolism of antibiotics, microbial virulence factors, and host responses.\n\nImportanceMicrobial infections are now recognized to be polymicrobial and personalized in nature. A comprehensive analysis and understanding of the factors underlying the polymicrobial and personalized nature of infections remains limited, especially in the context of the host. By visualizing microbiomes and metabolomes of diseased human lungs, we describe how different the chemical environments are between hosts that are dominated by the same pathogen and how community interactions shape the chemical environment, or vice versa. We highlight that three-dimensional organ mapping are hypothesis building tools that allow us to design mechanistic studies aimed at addressing microbial responses to other microbes, the host, and pharmaceutical drugs.

microbiology↗

Chemical Impacts of the Microbiome Across Scales Reveal Novel Conjugated Bile Acids

A mosaic of cross-phyla chemical interactions occurs between all metazoans and their microbiomes. In humans, the gut harbors the heaviest microbial load, but many organs, particularly those with a mucosal surface, associate with highly adapted and evolved microbial consortia1. The microbial residents within these organ systems are increasingly well characterized, yielding a good understanding of human microbiome composition, but we have yet to elucidate the full chemical impact the microbiome exerts on an animal and the breadth of the chemical diversity it contributes2. A number of molecular families are known to be shaped by the microbiome including short-chain fatty acids, indoles, aromatic amino acid metabolites, complex polysaccharides, and host lipids; such as sphingolipids and bile acids3-11. These metabolites profoundly affect host physiology and are being explored for their roles in both health and disease. Considering the diversity of the human microbiome, numbering over 40,000 operational taxonomic units12, a plethora of molecular diversity remains to be discovered. Here, we use unique mass spectrometry informatics approaches and data mapping onto a murine 3D-model13-15 to provide an untargeted assessment of the chemical diversity between germ-free (GF) and colonized mice (specific-pathogen free, SPF), and report the finding of novel bile acids produced by the microbiome in both mice and humans that have evaded characterization despite 170 years of research on bile acid chemistry16.

microbiology↗

MASST: A Web-based Basic Mass Spectrometry Search Tool for Molecules to Search Public Data.

CorrespondenceWe introduce a web-enabled small-molecule mass spectrometry (MS) search engine. To date, no tool can query all the public small-molecule tandem MS data in metabolomics repositories, greatly limiting the utility of these resources in clinical, environmental and natural product applications. Therefore, we introduce a Mass Spectrometry Search Tool (MASST) (https://proteosafe-extensions.ucsd.edu/masst/), that enables the discovery of molecular relationships among accessible public metabolomics and natural product tandem mass spectrometry data (MS/MS).

bioinformatics↗