Genedata Inc.

Lexington, MA, United States

Genedata Inc.

Lexington, MA, United States
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Yang D.,Taishan Medical University | Song D.,Tianjin University of Science and Technology | Kind T.,University of California at Davis | Ma Y.,University of California at Davis | And 3 more authors.
PLoS ONE | Year: 2015

Chlamydomonas reinhardtii accumulates lipids under complete nutrient starvation conditions while overall growth in biomass stops. In order to better understand biochemical changes under nutrient deprivation that maintain production of algal biomass, we used a lipidomic assay for analyzing the temporal regulation of the composition of complex lipids in C. reinhardtii in response to nitrogen and sulfur deprivation. Using a chip-based nanoelectrospray direct infusion into an ion trap mass spectrometer, we measured a diversity of lipid species reported for C. reinhardtii, including PG phosphatidylglycerols, PI Phosphatidylinositols, MGDG monogalactosyldiacylglycerols, DGDG digalactosyldiacylglycerols, SQDG sulfoquinovosyldiacylglycerols, DGTS homoserine ether lipids and TAG triacylglycerols. Individual lipid species were annotated by matching mass precursors and MS/MS fragmentations to the in-house LipidBlast mass spectral database and MS2Analyzer. Multivariate statistics showed a clear impact on overall lipidomic phenotypes on both the temporal and the nutrition stress level. Homoserine-lipids were found up-regulated at late growth time points and higher cell density, while triacyclglycerols showed opposite regulation of unsaturated and saturated fatty acyl chains under nutritional deprivation. Copyright: © 2015 Yang et al.


PubMed | Genedata Inc., King Abdulaziz University, Taishan Medical University, Tianjin University of Science and Technology and University of California at Davis
Type: Journal Article | Journal: PloS one | Year: 2015

Chlamydomonas reinhardtii accumulates lipids under complete nutrient starvation conditions while overall growth in biomass stops. In order to better understand biochemical changes under nutrient deprivation that maintain production of algal biomass, we used a lipidomic assay for analyzing the temporal regulation of the composition of complex lipids in C. reinhardtii in response to nitrogen and sulfur deprivation. Using a chip-based nanoelectrospray direct infusion into an ion trap mass spectrometer, we measured a diversity of lipid species reported for C. reinhardtii, including PG phosphatidylglycerols, PI Phosphatidylinositols, MGDG monogalactosyldiacylglycerols, DGDG digalactosyldiacylglycerols, SQDG sulfoquinovosyldiacylglycerols, DGTS homoserine ether lipids and TAG triacylglycerols. Individual lipid species were annotated by matching mass precursors and MS/MS fragmentations to the in-house LipidBlast mass spectral database and MS2Analyzer. Multivariate statistics showed a clear impact on overall lipidomic phenotypes on both the temporal and the nutrition stress level. Homoserine-lipids were found up-regulated at late growth time points and higher cell density, while triacyclglycerols showed opposite regulation of unsaturated and saturated fatty acyl chains under nutritional deprivation.


Kurland I.J.,Yeshiva University | Accili D.,Columbia University | Burant C.,University of Michigan | Fischer S.M.,Agilent Technologies | And 10 more authors.
Annals of the New York Academy of Sciences | Year: 2013

Diabesity has become a popular term to describe the specific form of diabetes that develops late in life and is associated with obesity. While there is a correlation between diabetes and obesity, the association is not universally predictive. Defining the metabolic characteristics of obesity that lead to diabetes, and how obese individuals who develop diabetes different from those who do not, are important goals. The use of large-scale omics analyses (e.g., metabolomic, proteomic, transcriptomic, and lipidomic) of diabetes and obesity may help to identify new targets to treat these conditions. This report discusses how various types of omics data can be integrated to shed light on the changes in metabolism that occur in obesity and diabetes. © 2013 New York Academy of Sciences.


Skalitzky C.A.,University of Wisconsin - Madison | Skalitzky C.A.,Hoffmann-La Roche | Martin J.R.,University of Florida | Martin J.R.,University of Colorado at Boulder | And 10 more authors.
Plant Physiology | Year: 2011

Proteins that are synthesized on cytoplasmic ribosomes but function within plastids must be imported and then targeted to one of six plastid locations. Although multiple systems that target proteins to the thylakoid membranes or thylakoid lumen have been identified, a system that can direct the integration of inner envelope membrane proteins from the stroma has not been previously described. Genetics and localization studies were used to show that plastids contain two different Sec systems with distinct functions. Loss-of-function mutations in components of the previously described thylakoid-localized Sec system, designated as SCY1 (At2g18710), SECA1 (At4g01800), and SECE1 (At4g14870) in Arabidopsis (Arabidopsis thaliana), result in albino seedlings and sucrose-dependent heterotrophic growth. Loss-of-function mutations in components of the second Sec system, designated as SCY2 (At2g31530) and SECA2 (At1g21650) in Arabidopsis, result in arrest at the globular stage and embryo lethality. Promoter-swap experiments provided evidence that SCY1 and SCY2 are functionally nonredundant and perform different roles in the cell. Finally, chloroplast import and fractionation assays and immunogold localization of SCY2- green fluorescent protein fusion proteins in root tissues indicated that SCY2 is part of an envelope-localized Sec system. Our data suggest that SCY2 and SECA2 function in Sec-mediated integration and translocation processes at the inner envelope membrane. © 2010 American Society of Plant Biologists.


Fernandez D.E.,University of Wisconsin - Madison | Wang C.-T.,University of Wisconsin - Madison | Wang C.-T.,National Taiwan University | Zheng Y.,University of Kentucky | And 5 more authors.
Plant Physiology | Year: 2014

Multiple factors, including the MADS-domain proteins AGAMOUS-LIKE15 (AGL15) and AGL18, contribute to the regulation of the transition from vegetative to reproductive growth. AGL15 and AGL18 were previously shown to act redundantly as floral repressors and upstream of FLOWERING LOCUS T (FT) in Arabidopsis (Arabidopsis thaliana). A series of genetic and molecular experiments, primarily focused on AGL15, was performed to more clearly define their role. agl15 agl18 mutations fail to suppress ft mutations but show additive interactions with short vegetative phase (svp) mutations in ft and suppressor of constans1 (soc1) backgrounds. Chromatin immunoprecipitation analyses with AGL15-specific antibodies indicate that AGL15 binds directly to the FT locus at sites that partially overlap those bound by SVP and FLOWERING LOCUS C. In addition, expression of AGL15 in the phloem effectively restores wild-type flowering times in agl15 agl18 mutants. When agl15 agl18 mutations are combined with agl24 svp mutations, the plants show upward curling of rosette and cauline leaves, in addition to early flowering. The change in leaf morphology is associated with elevated levels of FT and ectopic expression of SEPALLATA3 (SEP3), leading to ectopic expression of floral genes. Leaf curling is suppressed by sep3 and ft mutations and enhanced by soc1 mutations. Thus, AGL15 and AGL18, along with SVP and AGL24, are necessary to block initiation of floral programs in vegetative organs. © 2014 American Society of Plant Biologists. All rights reserved.


Schumacher A.,Genedata AG | Rujan T.,Genedata AG | Hoefkens J.,Genedata Inc.
Applied and Translational Genomics | Year: 2014

The integration and analysis of large datasets in translational research has become an increasingly challenging problem. We propose a collaborative approach to integrate established data management platforms with existing analytical systems to fill the hole in the value chain between data collection and data exploitation. Our proposal in particular ensures data security and provides support for widely distributed teams of researchers. As a successful example for such an approach, we describe the implementation of a unified single platform that combines capabilities of the knowledge management platform tranSMART and the data analysis system Genedata Analyst™. The combined end-to-end platform helps to quickly find, enter, integrate, analyze, extract, and share patient- and drug-related data in the context of translational R&D projects. © 2014.


Hoefkens J.,Genedata Inc. | Ceroni A.,Genedata GmbH | Haberl P.,Genedata GmbH | Taylor A.,Genedata AG
Chimica Oggi/Chemistry Today | Year: 2014

The biotherapeutics market has enjoyed exceptional growth in recent years. Comprehensive characterisations of biopharmaceuticals have become increasingly important, especially for regulatory submissions. With improvements in performance, sample throughput and sensitivity, Mass Spectrometry (MS) is replacing traditional methods in an increasing number of applications such as identification of Post-Translational Modifications (PTM) and glycosylation studies. However, the sheer volume of data produced by modern MS instruments has led to a bottleneck in data processing. This article gives an overview of MS-based techniques currently used for the characterisation and analysis of biotherapeutics. It will specifically detail recent developments in bioinformatics that offer innovative approaches for greatly streamlining these processes. As an example, the article will discuss an alternative process for batch control.


Bushman D.M.,Scripps Research Institute | Bushman D.M.,University of California at San Diego | Kaeser G.E.,Scripps Research Institute | Kaeser G.E.,University of California at San Diego | And 8 more authors.
eLife | Year: 2015

Previous reports have shown that individual neurons of the brain can display somatic genomic mosaicism of unknown function. In this study, we report altered genomic mosaicism in single, sporadic Alzheimer's disease (AD) neurons characterized by increases in DNA content and amyloid precursor protein (APP) gene copy number. AD cortical nuclei displayed large variability with average DNA content increases of ∼8% over non-diseased controls that were unrelated to trisomy 21. Two independent single cell copy number analyses identified amplifications at the APP locus. The use of single cell qPCR identified up to 12 copies of APP in sampled neurons. Peptide nucleic acid (PNA) probes targeting APP, combined with super-resolution microscopy detected primarily single fluorescent signals of variable intensity that paralleled single-cell qPCR analyses. These data identify somatic genomic changes in single neurons, affecting known and unknown loci, which are increased in sporadic AD, and further indicate functionality for genomic mosaicism in the CNS. © Bushman et al.


Bush D.R.,Northeastern University | Bush D.R.,Genedata Inc. | Zang L.,Biogen | Belov A.M.,Northeastern University | And 2 more authors.
Analytical Chemistry | Year: 2016

New and improved methods are required for the enhanced characterization of complex biopharmaceuticals, especially those with charge and glycan heterogeneity. High resolution separation and mass spectrometry (MS) analysis of intact proteoforms can contribute significantly to the characterization of such proteins, many of which are glycoproteins. Here, we report on capillary zone electrophoresis (CZE) coupled via a commercial CESI sheathless interface to an Orbitrap ELITE MS for the intact analysis of recombinant human interferon-β1 (Avonex, rhIFN-β1), a biopharmaceutical with complex glycosylation at a single N-linked site. Using a cross-linked polyethylenimine coating, column efficiencies between 350,000 and 450,000 plates were produced, allowing separation based on charge and subtle hydrodynamic volume differences. A total of 138 proteoforms were found, and 55 were quantitated. Charge species due to deamidation and sialylation were separated by CZE. Given the high column efficiency, isobaric positional isomers of a single sialic acid on biantennary glycan antennae were resolved. Further, triantennary isomers (antenna on α(1-3) or α(1-6) arms) were separated and confirmed by exoglycosidase digestion. Proteoforms of the N-terminal cleavage of methionine were detected by precursor molecular weight and top-down ETD and HCD analysis of the reduced protein. Quantitative analysis suggested potential correlations between the methionine loss with the relative amount of the deamidation, as well as the level of deamidation with glycan structure. We demonstrate that high resolution CZE separation of intact glycoprotein species coupled to MS has significant potential for the in-depth characterization and quantitative analysis of biopharmaceutical proteoforms. © 2015 American Chemical Society.


PubMed | Genedata Inc. and Genedata AG
Type: Journal Article | Journal: Applied & translational genomics | Year: 2016

The integration and analysis of large datasets in translational research has become an increasingly challenging problem. We propose a collaborative approach to integrate established data management platforms with existing analytical systems to fill the hole in the value chain between data collection and data exploitation. Our proposal in particular ensures data security and provides support for widely distributed teams of researchers. As a successful example for such an approach, we describe the implementation of a unified single platform that combines capabilities of the knowledge management platform tranSMART and the data analysis system Genedata Analyst. The combined end-to-end platform helps to quickly find, enter, integrate, analyze, extract, and share patient- and drug-related data in the context of translational R&D projects.

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