Biology subjects

Sanchez, A.

Publications and source records attributed to Sanchez, A..

At least 37 records · Page 2Linked to original sources

bioRxiv2024

Towards a Taxonomy Machine. A Training Set of 5.6 Million Arthropod Images

The taxonomic identification of organisms from images is an active research area within the machine learning community. Current algorithms are very effective for object recognition and discrimination, but they require extensive training datasets to generate reliable assignments. This study releases 5.6 million images with representatives from 10 arthropod classes and 26 insect orders. All images were taken using a Keyence VHX-7000 Digital Microscope system with an automatic stage to permit high-resolution (4K) microphotography. Providing phenotypic data for 324,000 species derived from 48 countries, this release represents, by far, the largest dataset of standardized arthropod images. As such, this dataset is well suited for testing the efficacy of machine learning algorithms for identifying specimens to higher taxonomic categories.

bioinformatics↗

bioRxiv2024

Top-Down Proteomics Identifies Plasma Proteoform Signatures of Liver Cirrhosis Progression

Cirrhosis, advanced liver disease, affects 2-5 million Americans. While most patients have compensated cirrhosis and may be fairly asymptomatic, many decompensate and experience life-threatening complications such as gastrointestinal bleeding, confusion (hepatic encephalopathy), and ascites, reducing life expectancy from 12 to less than 2 years. Among patients with compensated cirrhosis, identifying patients at high risk of decompensation is critical to optimize care and reduce morbidity and mortality. Therefore, it is important to preferentially direct them towards specialty care which cannot be provided to all patients with cirrhosis. We used discovery Top-down Proteomics (TDP) to identify differentially expressed proteoforms (DEPs) in the plasma of patients with progressive stages of liver cirrhosis with the ultimate goal to identify candidate biomarkers of disease progression. In this pilot study, we identified 209 DEPs across three stages of cirrhosis (compensated, compensated with portal hypertension, and decompensated), of which 115 derived from proteins enriched in the liver at a transcriptional level and discriminated the three stages of cirrhosis. Enrichment analyses demonstrated DEPs are involved in several metabolic and immunological processes known to be impacted by cirrhosis progression. We have preliminarily defined the plasma proteoform signatures of cirrhosis patients, setting the stage for ongoing discovery and validation of biomarkers for early diagnosis, risk stratification, and disease monitoring. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=156 SRC="FIGDIR/small/599662v1_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@797e27org.highwire.dtl.DTLVardef@495bb7org.highwire.dtl.DTLVardef@2478a9org.highwire.dtl.DTLVardef@6dbc0a_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIPerformed a pilot top-down LC-MS/MS analysis to identify proteoforms (PFRs) in the plasma of patients with 3 progressive stages of liver cirrhosis. C_LIO_LIIdentified 2867 proteoforms (PFRs) and 209 differentially regulated proteoforms (DRPs) in the different stages of the disease. C_LIO_LIIdentified DRP profiles able to potentially distinguish early from late stages of the disease, including 115 liver-derived DRPs. C_LIO_LIFibrinogen alpha chain, haptoglobin, and Apo A-I are the proteins with the highest number of DRPs and represent potential candidate biomarkers of liver cirrhosis progression. C_LI

molecular biology↗

bioRxiv2024

Caldas meets Janzen: Thermal regimes of montane plants and implications for global patterns of speciation

The seasonality hypothesis posits that limited seasonal temperature variability in tropical mountains leads to greater climatic zonation along elevation gradients compared to temperate regions. This is predicted to result in narrow thermal tolerances and restricted dispersal for organisms, which may reduce gene flow and increase opportunities for climate-associated parapatric or allopatric speciation in tropical mountains relative to temperate-zone mountains. This hypothesis has been tested in various animal groups but not in plants. We examine the elevational and thermal ranges of pairs of sister species of angiosperms from mountains worldwide. Our findings indicate no significant difference in the breadth and overlap of elevational ranges between tropical and temperate species. However, tropical species have narrower thermal ranges and show greater similarity in these ranges between sister species compared to temperate ones. Such narrow thermal specialization in tropical plants facilitates population divergence and allopatric speciation within thermal zones more than in temperate species.

evolutionary biology↗

bioRxiv2024

Full factorial construction of synthetic microbial communities

Constructing combinatorially complete species assemblages is often necessary to dissect the complexity of microbial interactions and to find optimal microbial consortia. At the moment, this is accomplished through either painstaking, labor intensive liquid handling procedures, or through the use of state-of-the-art microfluidic devices. Here we present a simple, rapid, low-cost, and highly accessible liquid handling methodology for assembling all possible combinations of a library of microbial strains, which can be implemented with basic laboratory equipment. To demonstrate the usefulness of this methodology, we construct a combinatorially complete set of consortia from a library of eight Pseudomonas aeruginosa strains, and empirically measure the community-function landscape of biomass productivity, identify the highest yield community, and dissect the interactions that lead to its optimal function. This easy to implement, inexpensive methodology will make the assembly of combinatorially complete microbial consortia easily accessible for all laboratories.

ecology↗

bioRxiv2024

Predicting immune checkpoint therapy response in three independent metastatic melanoma cohorts

While Immune checkpoint inhibition (ICI) therapy shows significant efficacy in metastatic melanoma, only about 50% respond, lacking reliable predictive methods. We introduce a panel of six proteins aimed at predicting response to ICI therapy. Evaluating previously reported proteins in two untreated melanoma cohorts, we used a published predictive model (EaSIeR score) to identify potential proteins distinguishing responders and non-responders. Six proteins initially identified in the ICI cohort correlated with predicted response in the untreated cohort. Additionally, three proteins correlated with patient survival, both at the protein, and at the transcript levels, in an independent immunotherapy treated cohort. Our study identifies predictive biomarkers across three melanoma cohorts, suggesting their use in therapeutic decision-making. O_FIG O_LINKSMALLFIG WIDTH=164 HEIGHT=200 SRC="FIGDIR/small/592032v1_ufig1.gif" ALT="Figure 1"> View larger version (63K): org.highwire.dtl.DTLVardef@754668org.highwire.dtl.DTLVardef@1616263org.highwire.dtl.DTLVardef@827009org.highwire.dtl.DTLVardef@1899ba7_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2024

Identifying Ferroptosis Inducers, HDAC, and RTK Inhibitor Sensitivity in Melanoma Subtypes through Unbiased Drug Target Prediction

The utilization of PD1 and CTLA4 inhibitors has revolutionized the treatment of malignant melanoma (MM). However, resistance to targeted and immune-checkpoint-based therapies still poses a significant problem. Here we mine large scale MM proteogenomic data integrating it with MM cell line dependency screen, and drug sensitivity data to identify druggable targets and forecast treatment efficacy and resistance. Leveraging protein profiles from established MM subtypes and molecular structures of 82 cancer treatment drugs, we identified nine candidate hub proteins, mTOR, FYN, PIK3CB, EGFR, MAPK3, MAP4K1, MAP2K1, SRC and AKT1, across five distinct MM subtypes. These proteins serve as potential drug targets applicable to one or multiple MM subtypes. By analyzing transcriptomic data from 48 publicly accessible melanoma cell lines sourced from Achilles and CRISPR dependency screens, we forecasted 162 potentially targetable genes. We also identified genetic resistance in 260 genes across at least one melanoma subtype. In addition, we employed publicly available compound sensitivity data (Cancer Therapeutics Response Portal, CTRPv2) on the cell lines to assess the correlation of compound effectiveness within each subtype. We have identified 20 compounds exhibiting potential drug impact in at least one melanoma subtype. Remarkably, employing this unbiased approach, we have uncovered compounds targeting ferroptosis, that demonstrate a striking 30x fold difference in sensitivity among different subtypes. This implies that the proteogenomic classification of melanoma has the potential to predict sensitivity to ferroptosis compounds. Our results suggest innovative and novel therapeutic strategies by stratifying melanoma samples through proteomic profiling, offering a spectrum of novel therapeutic interventions and prospects for combination therapy. Highlights(1) Proteogenomic subtype classification can define the landscape of genetic dependencies in melanoma (2) Nine proteins from molecular subtypes were identified as potential drug targets for specified MM patients (3) 20 compounds identified that show potential effectiveness in at least one melanoma subtype (4) Proteogenomics can predict specific ferroptosis inducers, HDAC, and RTK Inhibitor sensitivity in melanoma subtypes O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=184 SRC="FIGDIR/small/579424v1_ufig1.gif" ALT="Figure 1"> View larger version (51K): org.highwire.dtl.DTLVardef@73dd77org.highwire.dtl.DTLVardef@d0cb8eorg.highwire.dtl.DTLVardef@1e4117forg.highwire.dtl.DTLVardef@38b727_HPS_FORMAT_FIGEXP M_FIG Graphical abstract C_FIG

cancer biology↗

bioRxiv2023

The hepatocyte Epidermal Growth Factor Receptor (EGFR) pathway regulates the cellular interactome within the liver fibrotic niche

Background & AimsLiver fibrosis is the consequence of chronic liver injury in the presence of an inflammatory component. Although the main executors of this activation are known, the mechanisms that lead to the inflammatory process that mediates the production of profibrotic factors are not well characterized. The Epidermal Growth Factor Receptor (EGFR) signaling in hepatocytes is essential for the regenerative process of the liver; however, its potential role in regulating the fibrotic niche is not yet clear. Approach & ResultsOur group generated a mouse model that expresses an inactive truncated form of the EGFR specifically in hepatocytes ({Delta}EGFR mice). Here, we have analyzed the response of WT and {Delta}EGFR mice to chronic treatment with CCl4. Resultsindicated that the hallmarks of liver fibrosis were attenuated in CCl4-treated {Delta}EGFR mice when compared to WT mice, coinciding with a faster resolution of the fibrotic process and an ameliorated damage. The absence of EGFR activity in hepatocytes induced changes in the pattern of immune cells in the liver, with a notable change in the population of M2 macrophages, more related to fibrosis resolution, as well as an increase in the population of lymphocytes related to eradication of the damage. Transcriptomic analysis of hepatocytes and secretome studies from extracellular media in in vitro studies allowed to elucidate the specific molecular mechanisms regulated by EGFR that mediate hepatocyte production of both pro-inflammatory and pro-fibrotic mediators. ConclusionsOur results support a pro-inflammatory and pro-fibrogenic role for the hepatocyte EGFR pathway during chronic liver damage.

pathology↗

bioRxiv2023

Metabolic similarity and the predictability of microbial community assembly

AbstractWhen microbial communities form, their composition is shaped by selective pressures imposed by the environment. Can we predict which communities will assemble under different environmental conditions? Here, we hypothesize that quantitative similarities in metabolic traits across metabolically similar environments lead to predictable similarities in community composition. To that end, we measured the growth rate and by-product profile of a library of proteobacterial strains in a large number of single nutrient environments. We found that growth rates and secretion profiles were positively correlated across environments when the supplied substrate was metabolically similar. By analyzing hundreds of in-vitro communities experimentally assembled in an array of different synthetic environments, we then show that metabolically similar substrates select for taxonomically similar communities. These findings lead us to propose and then validate a comparative approach for quantitatively predicting the effects of novel substrates on the composition of complex microbial consortia.

ecology↗

bioRxiv2023

Histopathology-assisted proteogenomics provides foundations for stratification of melanoma metastases

Here we describe the histopathology-driven proteogenomic landscape of 142 treatment-naive metastatic melanoma samples. We identified five proteomic subtypes that integrate the immune and stroma microenvironment components, and associate with clinical and histopathological parameters, providing foundations for an in-depth molecular classification of melanoma. Our study shows that BRAF V600 mutated melanomas display heterogeneous biology, where the presence of an oncogene-induced senescence-like phenotype improves patient survival. Therefore, we propose a mortality-risk-based stratification, which may contribute to a more personalized approach to patient treatment. We also found a strong association between tumor microenvironment composition, disease progression, and patient outcome supported by single-cell omic signatures that point to straightforward histopathological connective tissue-to-tumor ratio assessment for better informed medical decisions. A melanoma-associated signature of single amino acid variants (SAAV) responsible for remodeling the extracellular matrix was uncovered together with SAAV-derived neoantigen candidates as targets of anti-tumor immune responses. Overall, this study offers comprehensive stratifications of melanoma metastases that may help develop tailored strategies for diagnosing and treating the disease.

cancer biology↗

bioRxiv2023

Community ecology of phages on a clonal bacterial host

Bacteriophages are the most abundant and diverse biological entities on Earth, yet the ecological mechanisms that sustain this extraordinary diversity remain unclear. Here, we have discovered a general mechanism that allows phage diversity to outstrip the diversity of their bacterial hosts. We assembled and passaged dozens of diverse phage communities on a single, non-coevolving strain of Escherichia coli until the phage communities reached equilibrium. In all cases, we found multiple phage species coexisted stably, despite competition for a single, clonal host population. Coexistence within these communities was supported through host phenotypic heterogeneity, whereby phages specialized on cells adopting different growth phenotypes. Our experiments reveal a rich community ecology of bacteriophages where multiple phage species coexist and interact at the scale of a single bacterial host. One-Sentence SummaryDiverse communities of phages emerge stably and consistently on a clonal bacterial host, enabled by phenotypic heterogeneity.

microbiology↗

bioRxiv2023

Absence of chromosome axis proteins recruitment prevents meiotic recombination chromosome-wide in the budding yeast Lachancea kluyveri

Meiotic recombination shows broad variations across species and along chromosomes, and is often suppressed at and around genomic regions determining sexual compatibility such as mating type loci in fungi. Here we show that the absence of Spo11-DSBs and meiotic recombination on Lakl0C-left, the chromosome arm containing the sex locus of the Lachancea kluyveri budding yeast, results from the absence of recruitment of the two chromosome axis proteins Red1 and Hop1, essential for proper Spo11-DSBs formation. Furthermore, cytological observation of spread pachytene meiotic chromosomes reveals that Lakl0C-left does not undergo synapsis. However, we show that the behavior of Lakl0C-left is independent of its particularly early replication timing and is not accompanied by any peculiar chromosome structure as detectable by Hi-C in this yet poorly studied yeast. Finally, we observed an accumulation of heterozygous mutations on Lakl0C-left and a sexual dimorphism of the haploid meiotic offspring, supporting a direct effect of this absence of meiotic recombination on L. kluyveri genome evolution and fitness. Because suppression of meiotic recombination on sex chromosomes is widely observed across eukaryotes, the novel mechanism for recombination suppression described here may apply to other species, with the potential to impact sex chromosome evolution.

genetics↗

bioRxiv2023

Vitamin D deficiency induces erectile dysfunction: role of superoxide

Epidemiological studies suggest a relationship between vitamin D deficiency and erectile dysfunction (ED) but its causal relationship and the mechanism involved are unclear. Here we demonstrate that isolated corpora cavernosa (CC) from human donors with low vitamin D levels show reduced NO-dependent erectile function. This ED is also reproduced in vitamin D deficient rats and vitamin D receptor knockout mice in vivo and ex vivo and is associated with penile fibrosis. Vitamin D deficiency also blunts the response of CC to the phosphodiesterase 5 inhibitor sildenafil. CC from deficient rats show increased superoxide and their impaired erectile function is restored by superoxide scavengers. These results suggest that vitamin D deficiency induces ED via increased superoxide production.

pharmacology and toxicology↗

bioRxiv2023

Mesoscale DNA Features Impact APOBEC3A and APOBEC3B Deaminase Activity and Shape Tumor Mutational Landscapes

Antiviral DNA cytosine deaminases APOBEC3A and APOBEC3B are major sources of mutations in cancer by catalyzing cytosine-to-uracil deamination. APOBEC3A preferentially targets singlestranded DNAs, with a noted affinity for DNA regions that adopt stem-loop secondary structures. However, the detailed substrate preferences of APOBEC3A and APOBEC3B have been fully established, and the specific influence of the DNA sequence on APOBEC3A APOBEC3B deaminase activity remains to be investigated. Here, we find that APOBEC3B selectively targets DNA stem-loop structures, and they are distinct from those subjected deamination by APOBEC3A. We develop Oligo-seq, a novel in vitro sequencing-based to identify specific sequence contexts promoting APOBEC3A and APOBEC3B activity. Through this approach, we demonstrate that APOBEC3A an APOBEC3B deaminase activity is strongly regulated by specific sequences surrounding the targeted cytosine. Moreover, we identify structural features of APOBEC3B and APOBEC3A responsible for their substrate preferences. Importantly, we determine that APOBEC3B-induced mutations in hairpin-forming sequences within tumor genomes differ from the DNA stem-loop sequences mutated by APOBEC3A. Together, our study provides evidence that APOBEC3A and APOBEC3B can generate mutation landscapes in cancer genomes, driven by their unique substrate selectivity.

biochemistry↗

bioRxiv2023

Predictive microbial community changes across a temperature gradient

A central challenge in community ecology is predicting the effects of abiotic factors on community assembly. In particular, microbial communities play a central role in the ecosystem, but we do not understand how changing factors like temperature are going to affect community composition or function. One of the challenges is that we do not understand the mechanistic impacts of temperature on different metabolic strategies, nor how this metabolic plasticity could impact microbial interactions. Dissecting the contribution of environmental factors on microbial interactions in natural ecosystems is hindered by our understanding of microbial physiology and our ability to disentangle interactions from sequencing data. Studying the self-assembly of multiple communities in synthetic environments, here we are able to predict changes in microbial community composition based on metabolic responses of each functional group along a temperature gradient. This research highlights the importance of metabolic plasticity and metabolic trade-offs in predicting species interactions and community dynamics across abiotic gradients.

ecology↗

bioRxiv2023

Macroecological laws in experimental microbial systems

Ecology has historically benefited from the characterization of statistical patterns of biodiversity within and across communities, an approach known as macroecology. Within microbial ecology, macroecological approaches have identified universal patterns of diversity and abundance that can be captured by effective models. Experimentation has simultaneously played a crucial role, as the advent of high-replication community time-series has allowed researchers to investigate underlying ecological forces. However, there remains a gap between experiments performed in the laboratory and macroecological patterns documented in natural systems, as we do not know whether these patterns can be recapitulated in the lab and whether experimental manipulations produce macroecological effects. This work aims at bridging the gap between experimental ecology and macroecology. Using high-replication time-series, we demonstrate that microbial macroecological patterns observed in nature exist in a laboratory setting, despite controlled conditions, and can be unified under the Stochastic Logistic Model of growth (SLM). We find that demographic manipulations (e.g., migration) impact observed macroecological patterns. By modifying the SLM to incorporate said manipulations alongside experimental details (e.g., sampling), we obtain predictions that are consistent with macroecological outcomes. By combining high-replication experiments with ecological models, microbial macroecology can be viewed as a predictive discipline.

ecology↗

bioRxiv2023

Preliminary Development of a Robotic Hip-Knee Exoskeleton with 3D-Printed Backdrivable Actuators

Robotic exoskeletons can provide powered locomotor assistance and rehabilitation to persons with mobility impairments due to aging and/or physical disabilities. Here we present the preliminary development and systems integration of T-BLUE - a modular, bilateral robotic hip-knee exoskeleton with 3D-printed backdriveable actuators. We retrofitted commercially available passive postoperative orthoses with open-source 3D-printed actuators to minimize cost and improve accessibility. The actuators are of quasi-direct drive design with high-torque density brushless DC motors and low gearing (15:1 transmission ratio) for low output impedance and high backdrivability, therein allowing for energy-efficient and dynamic human-robot physical interaction and legged locomotion. The modular design allows the exoskeleton to be customized and adapted to different users (e.g., persons with lateral vs. bilateral mobility impairments) and different hip-knee joint configurations. The goals of this preliminary study were to describe our experience with regards to the repeatability of the open-source 3D-printed actuators in engineering practice and the feasibility of integrating the actuators into wearable robotics hardware. This qualitative research serves as a first step towards using the robotic exoskeleton to support the development and testing of novel controller designs and rehabilitation protocols for different locomotor activities of daily living. We are especially interested in populations that could benefit from partial locomotor assistance such as older adults and/or persons with osteoarthritis. Future research will involve benchtop testing to quantitatively evaluate the actuator performance in terms of dynamics and energy-efficiency.

bioengineering↗

bioRxiv2023

The architecture of metabolic networks constrains the evolution of microbial resource hierarchies

Microbial strategies for resource use are an essential determinant of their fitness in complex habitats. When facing environments with multiple nutrients, microbes often use them sequentially according to a preference hierarchy, resulting in well-known patterns of diauxic growth. In theory, the evolutionary diversification of metabolic hierarchies could represent a mechanism supporting coexistence and biodiversity by enabling temporal segregation of niches. Despite this ecologically critical role, the extent to which substrate preference hierarchies can evolve and diversify remains largely unexplored. Here we used genome-scale metabolic modeling to systematically explore the evolution of metabolic hierarchies across a vast space of metabolic network genotypes. We find that only a limited number of metabolic hierarchies can readily evolve, corresponding to the most commonly observed hierarchies in genome-derived models. We further show how the evolution of novel hierarchies is constrained by the architecture of central metabolism, which determines both the propensity to change ranks between pairs of substrates and the effect of specific reactions on hierarchy evolution. Our analysis sheds light on the genetic and mechanistic determinants of microbial metabolic hierarchies, opening new research avenues to understand their evolution, evolvability and ecology.

evolutionary biology↗

bioRxiv2023

Distribution of the invasive Anisandrus maiche (Coleoptera: Scolytinae) in Switzerland, first record in Europe of its ambrosia fungus Ambrosiella cleistominuta, and its new association with Xylosandrus crassiusculus

In 2022, two independent insect surveys in canton Ticino (southern Switzerland) revealed the widespread occurrence of the invasive ambrosia beetle Anisandrus maiche from southern to central-upper Ticino. This species is native to east Asia and has previously been found as a non-native invasive species in the United States, Canada, western Russia, Ukraine and, in 2021, in northern Italy. Here, we present the results of several trapping studies using different trap types (bottle traps, funnel traps and Polytrap intercept traps) and attractants and a map of the distribution of the species. In total, 685 specimens of A. maiche, all female, were trapped, and the identity of selected individuals was confirmed by morphological and molecular identification based on three mitochondrial and nuclear markers (COI, 28S and CAD). Traps checked from early April to early September 2022 in intervals of two to four weeks showed that flights of A. maiche occurred mainly from June to mid-August. Isolation of fungal associates of A. maiche from beetles trapped alive revealed the presence of four fungal species, including the ambrosia fungus Ambrosiella cleistominuta, the known mutualists of A. maiche. The identity of A. cleistominuta was confirmed by comparing DNA sequences of its nuclear, internal transcribed spacer (ITS) gene with reference sequences in NCBI and BOLDSYSTEMS. This represents the first record of A. cleistominuta in Europe. Ambrosiella cleistominuta was also found in association with another non-native invasive ambrosia beetle, Xylosandrus crassiusculus, at a botanic garden in central Ticino. As ambrosia beetles usually show a high degree of fidelity with only one mutualistic fungus (in the case of X. crassiusculus normally Ambrosiella roeperi), this association is highly unusual and probably the result of lateral transfer among these non-native invasive species. Of the other fungal associates isolated from A. maiche in Ticino, Fusarium lateritium is of note as there is a possibility that A. maiche could act as a vector of this plant pathogen. We highlight several research needs that should be addressed to gain insight into the potential impact of these non-native species and to overcome problems with heteroplasmy in COI sequences in studies of invasion and population genetics of ambrosia beetles.

ecology↗