58 research outputs found

    Statistical HOmogeneous Cluster SpectroscopY (SHOCSY): An Optimized Statistical Approach for Clustering of <sup>1</sup>H NMR Spectral Data to Reduce Interference and Enhance Robust Biomarkers Selection

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    We propose a novel statistical approach to improve the reliability of <sup>1</sup>H NMR spectral analysis in complex metabolic studies. The Statistical HOmogeneous Cluster SpectroscopY (SHOCSY) algorithm aims to reduce the variation within biological classes by selecting subsets of homogeneous <sup>1</sup>H NMR spectra that contain specific spectroscopic metabolic signatures related to each biological class in a study. In SHOCSY, we used a clustering method to categorize the whole data set into a number of clusters of samples with each cluster showing a similar spectral feature and hence biochemical composition, and we then used an enrichment test to identify the associations between the clusters and the biological classes in the data set. We evaluated the performance of the SHOCSY algorithm using a simulated <sup>1</sup>H NMR data set to emulate renal tubule toxicity and further exemplified this method with a <sup>1</sup>H NMR spectroscopic study of hydrazine-induced liver toxicity study in rats. The SHOCSY algorithm improved the predictive ability of the orthogonal partial least-squares discriminatory analysis (OPLS-DA) model through the use of “truly” representative samples in each biological class (i.e., homogeneous subsets). This method ensures that the analyses are no longer confounded by idiosyncratic responders and thus improves the reliability of biomarker extraction. SHOCSY is a useful tool for removing irrelevant variation that interfere with the interpretation and predictive ability of models and has widespread applicability to other spectroscopic data, as well as other “omics” type of data

    Cell Orientation Gradients on an Inverse Opal Substrate

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    The generation of cell gradients is critical for understanding many biological systems and realizing the unique functionality of many implanted biomaterials. However, most previous work can only control the gradient of cell density and this has no effect on the gradient of cell orientation, which has an important role in regulating the functions of many connecting tissues. Here, we report on a simple stretched inverse opal substrate for establishing desired cell orientation gradients. It was demonstrated that tendon fibroblasts on the stretched inverse opal gradient showed a corresponding alignment along with the elongation gradient of the substrate. This “random-to-aligned” cell gradient reproduces the insertion part of many connecting tissues, and thus, will have important applications in tissue engineering

    Natural Mutagenesis-Enabled Global Proteomic Study of Metabolic and Carbon Source Implications in Mutant Thermoacidophillic Archaeon <i>Sulfolobus solfataricus</i> PBL2025

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    The thermoacidophilic crenarchaeon <i>Sulfolobus solfataricus</i> has been widely used as a model organism for archaeal systems biology research. Investigation using its spontaneous mutant PBL2025 provides an effective metabolic baseline to study subsequent mutagenesis-induced functional process shifts as well as changes in feedback inhibitions. Here, an untargeted metabolic investigation using quantitative proteomics and metabolomics was performed to correlate changes in <i>S. solfataricus</i> strains P2 against PBL2025 and under both glucose and tryptone. The study is combined with pathway enrichment analysis to identify prominent proteins with differential stoichiometry. Proteome level quantification reveals that over 20% of the observed overlapping proteome is differentially expressed under these conditions. Metabolic-induced differential expressions are observed along the central carbon metabolism, along with 12 other significantly regulated pathways. Current findings suggest that PBL2025 is able to compensate through the induction of carbon metabolism, as well as other anabolic pathways such as Val, Leu and iso-Leu biosynthesis. Studying protein abundance changes after changes in carbon sources also reveals distinct differences in metabolic strategies employed by both strains, whereby a clear down-regulation of carbohydrate and nucleotide metabolism is observed for P2, while a mixed response through down-regulation of energy formation and up-regulation of glycolysis is observed for PBL2025. This study contributes, to date, the most comprehensive network of changes in carbohydrate and amino acid pathways using the complementary systems biology observations at the protein and metabolite levels. Current findings provide a unique insight into molecular processing changes through natural (spontaneous) metabolic rewiring, as well as a systems biology understanding of the metabolic elasticity of thermoacidophiles to environmental carbon source change, potentially guiding more efficient directed mutagenesis in archaea

    Conjunction analysis of the brain activation patterns of SN and MN compared with those of UN reveals that the MPFC, ACC, and SFG are activated both in SN and MN conditions.

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    <p>Conjunction analysis of the brain activation patterns of SN and MN compared with those of UN reveals that the MPFC, ACC, and SFG are activated both in SN and MN conditions.</p

    Brain activations shown in various contrasts (p< 0.05, two-tail).

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    <p>Note: <i>X</i>, <i>Y</i>, and <i>Z</i> are Talairach coordinates; MPFC = medial prefrontal cortex; ACC = anterior cingulate cortex; IFG = inferior frontal gyrus; MTG = middle temporal gyrus; TPJ =  temporoparietal junction. * corrected for multiple comparisons.</p

    Brain activations shown in the conjunction analysis (cluster level).

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    <p>Note: <i>X</i>, <i>Y</i>, and <i>Z</i> are Talairach coordinates; MPFC = medial prefrontal cortex; ACC = anterior cingulate cortex; SFG = superior frontal gyrus.</p

    DataSheet_1_Single-cell analyses reveal the therapeutic effects of ATHENA and its mechanism in a rhabdomyosarcoma patient.xlsx

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    BackgroundWhole-cell tumor vaccines tend to suffer from low immunogenicity. Our previous study showed that irradiated lung cancer cell vaccines in mouse models enhance antitumor efficacy by eliciting an intensive T cells response and improving immunogenicity. Based on these findings, we developed an improved whole-cell tumor vaccine, Autologous Tumor Holo antigEn immuNe Activation (ATHENA).MethodsIn this study, we report the successful treatment of a 6-year-old male diagnosed with meningeal rhabdomyosarcoma with pulmonary and liver metastases using ATHENA. After 6 cycles of therapy, PET/CT showed the therapeutic efficacy of ATHENA. We profiled the immune response by single-cell RNA sequencing (scRNA-seq). Flow cytometry analysis was implemented to validate the status transitions of CD8+ T cells.ResultsIn CD8+ T cells, the exhausted status was weakened after treatment. The exhausted CD4+ T cells shifted towards the central memory phenotype after the treatment. Breg cells were converted to Plasma or Follicular B cells. Survival analysis for pan-cancer and transcription factor analysis indicated that such T cell and B cell transitions represent the recovery of antitumoral adaptive immune response. We validated that the proportion of CD279+CD8+ T cells were reduced and the expression of CD44 molecule was upregulated by flow cytometry assay.ConclusionSuch studies not only show that ATHENA therapy may be a promising alternative treatment for tumor patients but provide a novel idea to analyses the mechanisms of rare cases or personalized cancer treatment.</p
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