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Kim, M.

Publications and source records attributed to Kim, M..

At least 181 records · Page 10Linked to original sources
bioRxiv2024

Proteostasis Landscapes of Selective versus Poorly Responsive CFTR Variants Reveals Structural Vulnerabilities to Correction

Cystic Fibrosis (CF) is a lethal genetic disorder caused by variants in CF transmembrane conductance regulator (CFTR). Many variants are treatable with correctors, which enhance the folding and trafficking of CFTR. However, approximately 3% of persons with CF harbor poorly responsive variants. Here, we used affinity purification mass spectrometry proteomics to profile the protein homeostasis (proteostasis) changes of CFTR variants during correction to assess modulated interactions with protein folding and maturation pathways. Responsive variant interactions converged on similar proteostasis pathways during correction. In contrast, poorly responsive variants subtly diverged, revealing a partial restoration of protein quality control surveillance and partial correction. Computational structural modeling showed that corrector VX-445 failed to confer enough NBD1 stability to poor responders. NBD1 secondary stabilizing mutations rescued poorly responsive variants, revealing structural vulnerabilities in NBD1 required for treating poor responders. Our study provides a framework for discerning the underlying protein quality control and structural defects of CFTR variants not reached with existing drugs to expand therapeutics to all susceptible CFTR variants. SIGNIFICANCE STATEMENTCystic Fibrosis (CF) is a lethal genetic disease with variants leading to misfolding of an anion channel protein. Enhancing productive channel folding using a novel class of small molecules called correctors has emerged as the current CF treatment paradigm. However, correctors fail to reach all patient variants. Using high throughput interactomics, Rosetta simulations, and biochemical trafficking assays, this study demonstrates poorly responsive CF variants experience diverse misfolding pathways caused by structural defects in the core of a nucleotide-binding domain. Stabilizing secondary mutations in this domain rescues poorly responsive variants, paving the way for mechanistic-based therapeutic development for untreatable CF variants and future protein misfolding corrector drugs. COMPETING INTERESTSThe authors declare no competing interests.

biochemistry↗
bioRxiv2024

The maturation of infant and toddler visual cortex neural activity and associations with fine motor performance

Our understanding of how visual cortex neural processes mature during infancy and toddlerhood is limited. Using magnetoencephalography (MEG), the present study investigated the development of visual evoked responses (VERs) in both cross-sectional and longitudinal samples of infants and toddlers 2 months to 3 years. Brain space analyses focused on N1m and P1m latency, as well as the N1m-to-P1m amplitude. Associations between VER measures and developmental quotient (DQ) scores in the cognitive/visual and fine motor domains were also examined. Results showed a nonlinear decrease in N1m and P1m latency as a function of age, characterized by rapid changes followed by slower progression, with the N1m latency plateauing at 6-7 months and the P1m latency plateauing at 8-9 months. The N1m-to-P1m amplitude also exhibited a non-linear decrease, with strong responses observed in younger infants ([~]2-3 months) and then a gradual decline. Associations between N1m and P1m latency and fine motor DQ scores were observed, suggesting that infants with faster visual processing may be better equipped to perform fine motor tasks. The present findings advance our understanding of the maturation of the infant visual system and highlight the relationship between the maturation of visual system and fine motor skills. HighlightsO_LIThe infant N1m and P1m latency shows a nonlinear decrease. C_LIO_LIN1m latency decreases precede P1m latency decreases. C_LIO_LIN1m-to-P1m amplitude shows a nonlinear decrease, with stronger responses in younger than older infants. C_LIO_LIN1m and P1m latency are associated with fine motor DQ. C_LI

neuroscience↗
bioRxiv2024

Scalable electron tomography for connectomics

We demonstrate limited-tilt, serial section electron tomography (ET), which can non-destructively map brain circuits over large 3D volumes and reveal high-resolution, supramolecular details within subvolumes of interest. We show accelerated ET imaging of thick sections (>500 nm) with the capacity to resolve key features of neuronal circuits including chemical synapses, endocytic structures, and gap junctions. Furthermore, we systematically assessed how imaging parameters affect image quality and speed to enable connectomic-scale projects.

neuroscience↗
bioRxiv2024

Functional and structural maturation of auditory cortex from 2 months to 2 years old

In school-age children, the myelination of the auditory radiation thalamocortical pathway is associated with the latency of auditory evoked responses, with the myelination of thalamocortical axons facilitating the rapid propagation of acoustic information. Little is known regarding this auditory system function-structure association in infants and toddlers. The present study tested the hypothesis that maturation of auditory radiation white-matter microstructure (e.g., fractional anisotropy (FA); measured using diffusion-weighted MRI) is associated with the latency of the infant auditory response (P2m measured using magnetoencephalography, MEG) in a cross-sectional (2 to 24 months) as well as longitudinal cohort (2 to 29 months) of typically developing infants and toddlers. In the cross-sectional sample, non-linear maturation of P2m latency and auditory radiation diffusion measures were observed. After removing the variance associated with age in both P2m latency and auditory radiation diffusion measures, auditory radiation still accounted for significant variance in P2m latency. In the longitudinal sample, latency and FA associations could be observed at the level of a single child. Findings provide strong support for a contribution of auditory radiation white matter to rapid cortical auditory encoding processes in infants.

neuroscience↗
bioRxiv2024

Therapeutic potential of SOX9 dysruption in Combined Hepatocellular Carcinoma-Cholangiocarcinoma

Combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CCA) represents a challenging subtype of primary liver cancer with limited treatment options and a poor prognosis. Recently, we and others have highlighted the context-dependent roles of the biliary-specific transcription factor SOX9 in the pathogenesis of liver cancers using various Cre applications in Sox9(flox/flox) strains, to achieve elimination for exon 2 and 3 of the Sox9 gene locus as a preventive manner. Here, we reveal the contrasting responses of developmental Sox9 elimination using Alb-Cre;Sox9(flox/flox) (Sox9 LKO) versus CRISPR/Cas9-based tumor specific acute Sox9 CKO in SB-HDTVI-based Akt-YAP1 and Akt-NRAS cHCC-CCA formation. Sox9 LKO specifically abrogates the Akt-YAP1 CCA region while robustly stimulating the proliferation of remaining poorly differentiated HCC pertaining liver progenitor cell characteristics, whereas Sox9 CKO potently prevents Akt-YAP1 and Akt-NRAS cHCC-CCA development irrespective of fate of tumor cells compared to respective controls. Additionally, we find that Akt-NRAS, but not Akt-YAP1, tumor formation is partially dependent on the Sox9-Dnmt1 cascade. Pathologically, SOX9 is indispensable for Akt-YAP1-mediated HC-to-BEC/CCA reprogramming but required for the maintenance of CCA nodules. Lastly, therapeutic elimination of Sox9 using the OPN-CreERT2 strain combined with an inducible CRISPR/Cas9-based Sox9 iKO significantly reduces Akt-YAP1 cHCC-CCA tumor burden, similar to Sox9 CKO. Thus, we contrast the outcomes of acute Sox9 deletion with developmental Sox9 knockout models, emphasizing the importance of considering adaptation mechanisms in therapeutic strategies. This necessitates the careful consideration of genetic liver cancer studies using developmental Cre and somatic mutant lines, particularly for genes involved in hepatic commitment during development. Our findings suggest that SOX9 elimination may hold promise as a therapeutic approach for cHCC-CCA and underscore the need for further investigation to translate these preclinical insights into clinical applications.

cancer biology↗
bioRxiv2024

Clostridioides difficile binary toxin CDT induces biofilm-like persisting microcolonies

Clinical symptoms of Clostridioides difficile infection (CDI) range from diarrhea to pseudomembranous colitis. A major challenge in managing CDI is the high rate of relapse. Several studies correlate production of CDT binary toxin by clinical strains of Clostridioides difficile with higher relapse rates. Although the mechanism of action of CDT on host cells is known, its exact contribution to CDI is still unclear. To understand the physiological role of CDT during CDI, we established two hypoxic relevant intestinal models, Transwell and Microfluidic Intestine-on-Chip systems. Both were challenged with the epidemic strain UK1 CDT+ and its isogenic CDT- mutant. We report that CDT binary toxin induces mucin-associated microcolonies that increase C. difficile colonization and display biofilm-like properties by enhancing C. difficile resistance to vancomycin but not to fidaxomicin, a biofilm disrupting antibiotic. Importantly, biofilm- like CDT-dependent microcolonies were also observed in the caecum and colon of infected mice. Hence, our study shows that CDT toxin induces biofilm-like microcolonies, increasing C. difficile colonization and persistence.

microbiology↗
bioRxiv2024

Estropausal gut microbiota transplant improves ovarian function in adult mice

Decline in ovarian function with age not only affects fertility but is also linked to a higher risk of age-related diseases in women (e.g. osteoporosis, dementia). Intriguingly, earlier menopause is linked to shorter lifespan; however, the underlying molecular mechanisms of ovarian aging are not well understood. Recent evidence suggests the gut microbiota may influence ovarian health. In this study, we characterized ovarian aging associated microbial profiles in mice and investigated the effect of the gut microbiome from young and estropausal female mice on ovarian health through fecal microbiota transplantation. We demonstrate that the ovarian transcriptome can be broadly remodeled after heterochronic microbiota transplantation, with a reduction in inflammation-related gene expression and trends consistent with transcriptional rejuvenation. Consistently, these mice exhibited enhanced ovarian health and increased fertility. Using metagenomics-based causal mediation analyses and serum untargeted metabolomics, we identified candidate microbial species and metabolites that may contribute to the observed effects of fecal microbiota transplantation. Our findings reveal a direct link between the gut microbiota and ovarian health.

physiology↗
bioRxiv2024

Mathematical model of intestinal lipolysis of a long-chain triglyceride

Lipids are an important component of food and oral drug formulations. Upon release into gastrointestinal fluids, triglycerides, common components of foods and drug delivery systems, form emulsions and are digested into simpler amphiphilic lipids (e.g., fatty acids) that can associate with intestinal bile micelles and impact their drug solubilization capacity. Digestion of triglycerides is dynamic and dependent on lipid quantity and type, and quantities of other components in the intestinal environment (e.g., bile salts, lipases). The ability to predict lipid digestion kinetics in the intestine could enhance understanding of lipid impact on the fate of co-administered compounds (e.g., drugs, nutrients). In this study, we present a kinetic model that can predict the lipolysis of emulsions of triolein, a model long-chain triglyceride, as a function of triglyceride amount, droplet size, and quantity of pancreatic lipase in an intestinal environment containing bile micelles. The model is based on a Ping Pong Bi Bi mechanism coupled with quantitative analysis of partitioning of lipolysis products in colloids, including bile micelles, in solution. The agreement of lipolysis model predictions with experimental data suggests that the mechanism and proposed assumptions adequately represent triglyceride digestion in a simulated intestinal environment. In addition, we demonstrate the value of such a model over simpler, semi-mechanistic models reported in the literature. This lipolysis framework can serve as a basis for modeling digestion kinetics of different classes of triglycerides and other complex lipids as relevant in food and drug delivery systems.

bioengineering↗
bioRxiv2024

Distraction Impact of Concurrent Conversation on Event-Related Potential Based Brain-Computer Interfaces

ObjectiveThis study investigates the impact of conversation on the performance of visual event-related potential (ERP)-based brain-computer interfaces (BCIs), considering distractions in real life environment. The research aims to understand how cognitive distractions from speaking and listening activities affect ERP-BCI performance. ApproachThe experiment employs a dual-task paradigm where participants control a smart light using visual ERP-BCIs while simultaneously conducting speaking or listening tasks. Main resultsThe findings reveal that speaking notably degrades BCI accuracy and the amplitude of ERP components, while increases the latency variability of ERP components and occipital alpha power. In contrast, listening and simple syllable repetition tasks have a lesser impact on these variables. The results suggest that speaking activity significantly distracts visual attentional processes critical for BCI operation SignificanceThis study highlights the need to take distractions by daily conversation into account of the design and implementation of ERP-BCIs.

bioengineering↗
bioRxiv2024

Neuron-derived Prox1 suppresses injury-induced reprogramming of Muller glia to proliferative retinal progenitor cells

Individuals with retinal degenerative diseases face significant obstacles in restoring normal vision due to the inability to regenerate degenerated retinal cells. While retinal neurons can be regenerated from Muller glia (MG) in cold-blooded vertebrates, this regenerative ability is lacking in mammals, indicating the limited competence of mammalian MG for retinal regeneration. In this study, we elucidate the role of prospero-related homeobox 1 (Prox1) in rendering the mammalian retina incompetent for MG-derived regeneration. Prox1 accumulates in MG in the degenerating human and mouse retinas but not in those in the regenerating zebrafish retina. Strikingly, Prox1 in mouse MG originated from neighboring retinal neurons through intercellular protein transfer. Consequently, inhibition of Prox1 transfer to MG enables the reprogramming of MG into proliferative retinal progenitor cells in injured mouse retinas. Furthermore, we succeeded in regenerating retinal neurons and delaying vision loss in retinitis pigmentosa disease model in mice by adenoassociated viral gene delivery of an anti-Prox1 antibody that sequesters extracellular Prox1 in the mouse retina. Taken together, our findings highlight the therapeutic potential of anti-Prox1 therapy in restoring the regenerative potential of the mammalian retina.

developmental biology↗
bioRxiv2024

Loss of VHL-mediated pRb regulation promotes clear cell renal cell carcinoma

The von Hippel-Lindau (VHL) tumor suppressor is a component of E3 ubiquitin ligase complexes that target cellular substrates for proteasome-mediated degradation. VHL inactivation by genetic aberrations is observed in most sporadic cases of clear cell renal cell carcinoma (ccRCC). VHL loss leads to constitutive stabilization of E3 ligase targets, including hypoxia inducible factor (HIF), in VHL-associated tumors. HIF stabilization upon VHL loss promotes transactivation of hypoxia responsive genes, which contributes to ccRCC development. However, several HIF-independent VHL targets have also been implicated in the promotion of tumorigenesis. Using proximity labeling to identify proteasomal VHL interactors, we identified retinoblastoma protein (pRb) as a novel substrate of VHL. Mechanistically, VHL interacts with pRb in an oxygen-sensitive manner, promoting its ubiquitin-mediated degradation. Concordantly, VHL-inactivation results in pRb hyperstabilization. Functionally, the hyperstabilization of pRb in ccRCC promoted tumorigenesis in vitro and in mouse models. We also show that downstream transcriptional changes induced by pRb hyperstabilization may contribute to ccRCC tumor development. Together, our findings reveal a novel VHL-related pathway which can be therapeutically targeted to inhibit ccRCC tumor development.

cancer biology↗
bioRxiv2024

Seq-Scope Protocol: Repurposing Illumina Sequencing Flow Cells for High-Resolution Spatial Transcriptomics

Spatial transcriptomics (ST) technologies represent a significant advance in gene expression studies, aiming to profile the entire transcriptome from a single histological slide. These techniques are designed to overcome the constraints faced by traditional methods such as immunostaining and RNA in situ hybridization, which are capable of analyzing only a few target genes simultaneously. However, the application of ST in histopathological analysis is also limited by several factors, including low resolution, a limited range of genes, scalability issues, high cost, and the need for sophisticated equipment and complex methodologies. Seq-Scope--a recently developed novel technology--repurposes the Illumina sequencing platform for high-resolution, high-content spatial transcriptome analysis, thereby overcoming these limitations. Here we provide a detailed step-by-step protocol to implement Seq-Scope with an Illumina NovaSeq 6000 sequencing flow cell that allows for the profiling of multiple tissue sections in an area of 7 mm x 7 mm or larger. In addition to detailing how to prepare a frozen tissue section for both histological imaging and sequencing library preparation, we provide comprehensive instructions and a streamlined computational pipeline to integrate histological and transcriptomic data for high-resolution spatial analysis. This includes the use of conventional software tools for single cell and spatial analysis, as well as our recently developed segmentation-free method for analyzing spatial data at submicrometer resolution. Given its adaptability across various biological tissues, Seq-Scope establishes itself as an invaluable tool for researchers in molecular biology and histology. KEY POINTSO_LIThe protocol outlines a method for repurposing an Illumina NovaSeq 6000 flow cell as a spatial transcriptomics array, enabling the generation of high-resolution spatial datasets. C_LIO_LIThe protocol introduces a streamlined data analysis pipeline that produces a spatial digital gene expression matrix suitable for various single-cell and spatial transcriptome analysis methods. C_LIO_LIThe protocol allows for the capture of histology images from the same tissue section subjected to spatial transcriptomics analysis and allows users to precisely align the transcriptome dataset with the histological image using fiducial marks engraved on the flow cell surface. C_LIO_LILeveraging commonly available Illumina equipment, the protocol offers researchers ultra-high submicrometer resolution in spatial transcriptomics analysis with a comprehensive pipeline, rapid turnaround, cost efficiency, and versatility. C_LI

genomics↗
bioRxiv2024

Multifaceted roles of cohesin in regulating transcriptional loops

Cohesin is required for chromatin loop formation. However, its precise role in regulating gene transcription remains largely unknown. We investigated the relationship between cohesin and RNA Polymerase II (RNAPII) using single-molecule mapping and live-cell imaging methods in human cells. Cohesin-mediated transcriptional loops were highly correlated with those of RNAPII and followed the direction of gene transcription. Depleting RAD21, a subunit of cohesin, resulted in the loss of long-range (>100 kb) loops between distal (super-)enhancers and promoters of cell-type-specific genes. By contrast, the short-range (<50 kb) loops were insensitive to RAD21 depletion and connected genes that are mostly housekeeping. This result explains why only a small fraction of genes are affected by the loss of long-range chromatin interactions due to cohesin depletion. Remarkably, RAD21 depletion appeared to up-regulate genes located in early initiation zones (EIZ) of DNA replication, and the EIZ signals were amplified drastically without RAD21. Our results revealed new mechanistic insights of cohesins multifaceted roles in establishing transcriptional loops, preserving long-range chromatin interactions for cell-specific genes, and maintaining timely order of DNA replication.

genomics↗
bioRxiv2024

Metabolic Reprogramming by Mutant GNAS Creates an Actionable Dependency in Intraductal Papillary Mucinous Neoplasms of the Pancreas

ObjectiveOncogenic "hotspot" mutations of KRAS and GNAS are two major driver alterations in Intraductal Papillary Mucinous Neoplasms (IPMNs), which are bona fide precursors to pancreatic ductal adenocarcinoma. We previously reported that pancreas-specific KrasG12D and GnasR201C co-expression in p48Cre; KrasLSL-G12D; Rosa26LSL-rtTA; Tg (TetO-GnasR201C) mice ("Kras;Gnas" mice) caused development of cystic lesions recapitulating IPMNs. Here, we aim to unveil the consequences of mutant GnasR201C expression on phenotype, transcriptomic profile, and genomic dependencies. DesignWe performed multimodal transcriptional profiling (bulk RNA sequencing, single cell RNA sequencing, and spatial transcriptomics) in the "Kras;Gnas" autochthonous model and tumor-derived cell lines (Kras;Gnas cells), where GnasR201C expression is inducible. A genome-wide CRISPR/Cas9 screen was conducted to identify potential vulnerabilities in KrasG12D;GnasR201Cco-expressing cells. ResultsInduction of GnasR201C - and resulting G(s)alpha signaling - leads to the emergence of a gene signature of gastric (pyloric type) metaplasia in pancreatic neoplastic epithelial cells. CRISPR screening identified the synthetic essentiality of glycolysis-related genes Gpi1 and Slc2a1 in KrasG12D;GnasR201C co-expressing cells. Real-time metabolic analyses in Kras;Gnas cells and autochthonous Kras;Gnas model confirmed enhanced glycolysis upon GnasR201C induction. Induction of GnasR201C made KrasG12D expressing cells more dependent on glycolysis for their survival. Protein kinase A-dependent phosphorylation of the glycolytic intermediate enzyme PFKFB3 was a driver of increased glycolysis upon GnasR201C induction. ConclusionMultiple orthogonal approaches demonstrate that KrasG12D and GnasR201C co-expression results in a gene signature of gastric pyloric metaplasia and glycolytic dependency during IPMN pathogenesis. The observed metabolic reprogramming may provide a potential target for therapeutics and interception of IPMNs. SUMMARYO_ST_ABSWhat is already known on this topicC_ST_ABSO_LIActivating "hotspot" mutations of KRAS and GNAS are found in a majority of Intraductal Papillary Mucinous Neoplasms (IPMNs). C_LIO_LIExpression of mutant KRAS and GNAS drives development of IPMN-like cystic lesions in the murine pancreas that eventually progress to pancreatic ductal adenocarcinoma (PDAC). C_LI What this study addsO_LIMutant GNAS and the resulting aberrant G(s)alpha signaling drives a transcriptional signature of gastric (pyloric type) metaplasia in IPMNs with mucin production. C_LIO_LIAberrant G(s)alpha signaling enhances glycolysis via protein kinase A-dependent phosphorylation of the glycolytic enzyme PFKFB3. C_LIO_LIEnhanced glycolysis in KRAS;GNAS-mutated IPMN cells is validated via multiple orthogonal approaches in vitro and in vivo and represents an actionable metabolic vulnerability. C_LI How this study might affect research, practice or policyO_LIThe present study provides mechanistic insight into how aberrant G(s)alpha signaling alters the biology of Kras-mutant pancreatic epithelial neoplasia through metaplastic and metabolic reprogramming. C_LIO_LITargeting glycolysis in IPMNs may represent both a therapeutic avenue as well as an opportunity for intercepting progression to invasive cancer. C_LI

cancer biology↗
bioRxiv2024

Assessing Long-Term Stored Tissues for Multi-Omics Data Quality and Proteogenomics Suitability

As research into the complexities of cancer biology deepens, the integration of multi-omics analyses has emerged as a powerful approach to unravel the complex molecular basis of cancers. However, challenges related to sample availability, including size, collection procedures, and storage duration, hinder the broad application of this methodology. Despite these limitations, there is a growing interest in exploring the potential of archived samples to expand the scope of multi-omics research. Our study aims to investigate the impact of storage duration on the measurment in genomic, transcriptomic, and proteomic profiles of archived samples, demonstrating their viability for advancing our understanding of cancer biology. To comprehensively address these trends and limitations, we systematically examined archived samples collected over a decade, focusing on their transcriptomic, proteomic, and phosphoproteomic attributes. Analysis revealed intricate patterns and dynamic shifts, especially in long-term transcriptomic data, with observed declines in read counts related to protein coding and gene coverage. However, these changes did not compromise the fundamental gene expression landscape. Proteomic result also demonstrated that storage period did not significantly influence proteomic measurement. Comparisons of housekeeping gene (HKG) and housekeeping protein (HKP) expressions unveiled consistent transcriptomic levels across samples, while distinctive proteomic disparities between tumor and normal tissues. In conclusion, the challenges posed by limited sample availability in multi-omics studies can be partially overcome through the strategic integration of archived samples. While technical shifts were evident in certain aspects of transcriptomic data, core gene expression patterns remained robust, and the functionality of essential transcription factors (TFs) and kinases remained unaffected. These findings underscore the potential of archived samples as valuable resources for multi-omics research, providing a broader landscape for investigating cancer biology and paving the way for more comprehensive insights into this intricate field.

cancer biology↗
bioRxiv2024

Risk assessment predicts most of the salmonellosis risk in raw chicken parts is concentrated in those few products with high-levels of high-virulent serotypes of Salmonella

Salmonella prevalence has reduced in U.S. raw poultry products since adopting prevalence-based Salmonella performance standards, but human illnesses did not reduce proportionally. We used Quantitative Microbial Risk Assessment to evaluate public health risks of raw chicken parts contaminated with different levels of all Salmonella and specific high- and low-virulent serotypes. Lognormal Salmonella level distributions were fitted using data from 2012 USDA-FSIS Baseline Survey and 2023 USDA-FSIS HACCP verification sampling data. Three different dose-response (DR) models were used: Single DR for all serotypes, reduced virulence for Kentucky, multiple serotype- specific DR models. All scenarios found risk concentrated in the few products with high Salmonella levels. Using a single DR model with Baseline data (=-3.19, {sigma}=1.29), 68% and 37% of illnesses were attributed to the 0.7% and 0.06% of products > 1 and 10 CFU/g Salmonella, respectively. More recent HACCP data (=-4.85, {sigma}=2.44) showed that 99.9% and 99.6% of illnesses were attributed to the 2.3% and 0.8% of products > 1 and 10 CFU/g Salmonella, respectively. Scenarios with serotype-specific DR models showed more concentrated risk at higher levels. Baseline data showed 91.5% and 63.7% and HACCP data showed >99.9% and 99.9% of illnesses were attributed to products > 1 and 10 CFU/g Salmonella, respectively. Regarding serotypes, 0.003% and 0.3% of illnesses were attributed to the 0.2% and 0.7% of products with > 1 CFU/g of Kentucky, respectively, while 69% and 78.7% of illnesses were attributed to the 0.3% and 1.2% of products > 1 CFU/g containing either Enteritidis, Infantis, or Typhimurium using Baseline or HACCP input data, respectively. These results suggest public health risk in chicken parts is concentrated in the few finished products with high-levels and specifically high- levels of high-virulent serotypes. Low-virulent serotypes, such as Kentucky, are predicted to contribute to extremely few human cases.

microbiology↗
bioRxiv2024

Scvi-hub: an actionable repository for model-driven single cell analysis

The accumulation of single-cell omics datasets in the public domain has opened new opportunities for reusing and leveraging the vast amount of information they contain. Such uses, however, are complicated by the need for complex and resource-consuming procedures for data transfer, normalization and integration that must be addressed prior to any analysis. Here we present scvi-hub: a platform for efficiently sharing and accessing single-cell omics datasets using pre-trained probabilistic models. We demonstrate that scvi-hub allows immediate access to a slew of fundamental tasks like visualization, imputation, annotation, outlier detection, and deconvolution of new (query) datasets, using state of the art algorithms and with a requirement for storage and compute resources that is much lower compared to standard approaches. We also show that the pre-trained models enable efficient analysis and new discoveries with existing references, including large atlases such as the CZ CELLxGENE Discover Census. Scvi-hub is built within the scvi-tools open source environment and integrated into scverse. It provides powerful and readily available tools for utilizing a large collection of already-loaded datasets while also enabling easy inclusion of new datasets, thus putting the power of atlas-level analysis at the fingertips of a broad community of users.

bioinformatics↗