Tandem mass tag (TMT) is a multiplexing technology widely-used in proteomic research. It enables relative quantification of proteins from multiple biological samples in a single MS run with high efficiency and high throughput. However, experiments often require more biological replicates or conditions than can be accommodated by a single run, and involve multiple TMT mixtures and multiple runs. Such larger-scale experiments combine sources of biological and technical variation in patterns that are complex, unique to TMT-based workflows, and challenging for the downstream statistical analysis. These patterns cannot be adequately characterized by statistical methods designed for other technologies, such as label-free proteomics or transcriptomics. This manuscript proposes a general statistical approach for relative protein quantification in MS- based experiments with TMT labeling. It is applicable to experiments with multiple conditions, multiple biological replicate runs and multiple technical replicate runs, and unbalanced designs. It is based on a flexible family of linear mixed-effects models that handle complex patterns of technical artifacts and missing values. The approach is implemented in MSstatsTMT, a freely available open-source R/Bioconductor package compatible with data processing tools such as Proteome Discoverer, MaxQuant, OpenMS, and SpectroMine. Evaluation on a controlled mixture, simulated datasets, and three biological investigations with diverse designs demonstrated that MSstatsTMT balanced the sensitivity and the specificity of detecting differentially abundant proteins, in large-scale experiments with multiple biological mixtures.

Cross-linking MS (XL-MS) has been recognized as an effective source of information about protein structures and interactions. In contrast to regular peptide identification, XL-MS has to deal with a quadratic search space, where peptides from every protein could potentially be cross-linked to any other protein. To cope with this search space, most tools apply different heuristics for search space reduction. We introduce a new open-source XL-MS database search algorithm, OpenPepXL, which offers increased sensitivity compared with other tools. OpenPepXL searches the full search space of an XL-MS experiment without using heuristics to reduce it. Because of efficient data structures and built-in parallelization OpenPepXL achieves excellent runtimes and can also be deployed on large compute clusters and cloud services while maintaining a slim memory footprint. We compared OpenPepXL to several other commonly used tools for identification of noncleavable labeled and label-free cross-linkers on a diverse set of XL-MS experiments. In our first comparison, we used a data set from a fraction of a cell lysate with a protein database of 128 targets and 128 decoys. At 5% FDR, OpenPepXL finds from 7% to over 50% more unique residue pairs (URPs) than other tools. On data sets with available high-resolution structures for cross-link validation OpenPepXL reports from 7% to over 40% more structurally validated URPs than other tools. Additionally, we used a synthetic peptide data set that allows objective validation of cross-links without relying on structural information and found that OpenPepXL reports at least 12% more validated URPs than other tools. It has been built as part of the OpenMS suite of tools and supports Windows, macOS, and Linux operating systems. OpenPepXL also supports the MzIdentML 1.2 format for XL-MS identification results. It is freely available under a three-clause BSD license at https://openms.org/openpepxl.

Trypsin is the protease of choice in bottom-up proteomics. However, its application can be limited by the amino acid composition of target proteins and the pH of the digestion solution. In this study we characterize ProAlanase, a protease from the fungus Aspergillus niger that cleaves primarily on the C-terminal side of proline and alanine residues. ProAlanase achieves high proteolytic activity and specificity when digestion is carried out at acidic pH (1.5) for relatively short (2 h) time periods. To elucidate the potential of ProAlanase in proteomics applications, we conducted a series of investigations comprising comparative multi-enzymatic profiling of a human cell line proteome, histone PTM analysis, ancient bone protein identification, phosphosite mapping and de novo sequencing of a proline-rich protein and disulfide bond mapping in mAb. The results demonstrate that ProAlanase is highly suitable for proteomics analysis of the arginine- and lysine-rich histones, enabling high sequence coverage of multiple histone family members. It also facilitates an efficient digestion of bone collagen thanks to the cleavage at the C terminus of hydroxyproline which is highly prevalent in collagen. This allows to identify complementary proteins in ProAlanase- and trypsin-digested ancient bone samples, as well as to increase sequence coverage of noncollagenous proteins. Moreover, digestion with ProAlanase improves protein sequence coverage and phosphosite localization for the proline-rich protein Notch3 intracellular domain (N3ICD). Furthermore, we achieve a nearly complete coverage of N3ICD protein by de novo sequencing using the combination of ProAlanase and tryptic peptides. Finally, we demonstrate that ProAlanase is efficient in disulfide bond mapping, showing high coverage of disulfide-containing regions in a nonreduced mAb.

Over the past decade, modern methods of MS (MS) have emerged that allow reliable, fast and cost-effective identification of pathogenic microorganisms. Although MALDI-TOF MS has already revolutionized the way microorganisms are identified, recent years have witnessed also substantial progress in the development of liquid chromatography (LC)-MS based proteomics for microbiological applications. For example, LC-tandem MS (LC-MS²) has been proposed for microbial characterization by means of multiple discriminative peptides that enable identification at the species, or sometimes at the strain level. However, such investigations can be laborious and time-consuming, especially if the experimental LC-MS² data are tested against sequence databases covering a broad panel of different microbiological taxa. In this proof of concept study, we present an alternative bottom-up proteomics method for microbial identification. The proposed approach involves efficient extraction of proteins from cultivated microbial cells, digestion by trypsin and LC–MS measurements. Peptide masses are then extracted from MS¹ data and systematically tested against an in silico library of all possible peptide mass data compiled in-house. The library has been computed from the UniProt Knowledgebase covering Swiss-Prot and TrEMBL databases and comprises more than 12,000 strain-specific in silico profiles, each containing tens of thousands of peptide mass entries. Identification analysis involves computation of score values derived from correlation coefficients between experimental and strain-specific in silico peptide mass profiles and compilation of score ranking lists. The taxonomic positions of the microbial samples are then determined by using the best-matching database entries. The suggested method is computationally efficient – less than 2 mins per sample - and has been successfully tested by a test set of 39 LC-MS¹ peak lists obtained from 19 different microbial pathogens. The proposed method is rapid, simple and automatable and we foresee wide application potential for future microbiological applications.

Pathway analyses are key methods to analyze 'omics experiments. Nevertheless, integrating data from different 'omics technologies and different species still requires considerable bioinformatics knowledge.

Here we present the novel ReactomeGSA resource for comparative pathway analyses of multi-omics datasets. ReactomeGSA can be used through Reactome's existing web interface and the novel ReactomeGSA R Bioconductor package with explicit support for scRNA-seq data. Data from different species is automatically mapped to a common pathway space. Public data from ExpressionAtlas and Single Cell ExpressionAtlas can be directly integrated in the analysis. ReactomeGSA greatly reduces the technical barrier for multi-omics, cross-species, comparative pathway analyses.

We used ReactomeGSA to characterize the role of B cells in anti-tumor immunity. We compared B cell rich and poor human cancer samples from five of the Cancer Genome Atlas (TCGA) transcriptomics and two of the Clinical Proteomic Tumor Analysis Consortium (CPTAC) proteomics studies. B cell-rich lung adenocarcinoma samples lacked the otherwise present activation through NFkappaB. This may be linked to the presence of a specific subset of tumor associated IgG+ plasma cells that lack NFkappaB activation in scRNA-seq data from human melanoma. This showcases how ReactomeGSA can derive novel biomedical insights by integrating large multi-omics datasets.

The increasing consumption of high-fat foods combined with a lack of exercise is a major contributor to the burden of obesity in humans. Aerobic exercise such as running is known to provide metabolic benefits, but how the over-consumption of a high fat diet (HFD) and exercise interact is not well characterized at the molecular level. Here, we examined the plasma proteome in mice for the effects of aerobic exercise as both a treatment and as a preventative regime for animals on either HFD or a healthy control diet. This analysis detected large changes in the plasma proteome induced by the HFD, such as increased abundance of SERPINA7, ALDOB, and down-regulation of SERPINA1E, CFD (adipsin). Some of these changes were significantly reverted using exercise as a preventative measure, but not as a treatment regime. To determine if either the intensity, or duration, of exercise influenced the outcome, we compared high-intensity interval training (HIIT) and endurance running. Endurance running slightly out-performed HIIT exercise, but overall, both provided similar reversion in abundance of plasma proteins modulated by the high-fat diet including SERPINA7, APOE, SERPINA1E, and CFD. Finally, we compared the changes induced by over-consumption of HFD to previous data from mice fed an isocaloric high saturated fat (SFA) or polyunsaturated fat (PUFA) diet. This identified several common changes including increased APOC2 and APOE, but also highlighted changes specific for either over-consumption of HFD (ALDOB, SERPINA7, CFD), SFA-based diets (SERPINA1E), or PUFA-based diets (Haptoglobin - Hp). Together, these data highlight the importance of early intervention with exercise to revert HFD-induced phenotypes and suggest some of the molecular mechanisms leading to the changes in the plasma proteome generated by high fat diet consumption. Web-based interactive visualizations are provided for this dataset (larancelab.com/hfd-exercise), which give insight into diet and exercise phenotypic interactions on the plasma proteome.

We developed a simple and rapid method to enrich protein N-terminal peptides, in which the protease TrypN is first employed to generate protein N-terminal peptides without Lys or Arg and internal peptides with two positive charges at their N-termini, and then the N-terminal peptides with or without N-acetylation are separated from the internal peptides by strong cation exchange chromatography according to a retention model based on the charge/orientation of peptides. This approach was applied to 20 μg of human HEK293T cell lysate proteins to profile the N-terminal proteome. On average, 1,550 acetylated and 200 unmodified protein N-terminal peptides were successfully identified in a single LC/MS/MS run with less than 3% contamination with internal peptides, even when we accepted only canonical protein N-termini registered in the Swiss-Prot database. Since this method involves only two steps, protein digestion and chromatographic separation, without the need for tedious chemical reactions, it should be useful for comprehensive profiling of protein N-termini, including proteoforms with neo-N-termini.

Open searching has proven to be an effective strategy for identifying both known and unknown modifications in shotgun proteomics experiments. Rather than being limited to a small set of user-specified modifications, open searches identify peptides with any mass shift that may correspond to a single modification or a combination of several modifications. Here we present PTM-Shepherd, a bioinformatics tool that automates characterization of PTM profiles detected in open searches based on attributes such as amino acid localization, fragmentation spectra similarity, retention time shifts, and relative modification rates. PTM-Shepherd can also perform multi-experiment comparisons for studying changes in modification profiles, e.g. in data generated in different laboratories or under different conditions. We demonstrate how PTM-Shepherd improves the analysis of data from formalin-fixed paraffin-embedded samples, detects extreme underalkylation of cysteine in some datasets, discovers an artefactual modification introduced during peptide synthesis, and uncovers site-specific biases in sample preparation artifacts in a multi-center proteomics profiling study.

Police in northeast Ohio have placed a school resource officer on unpaid leave for activating a Taser to wake up a sleeping student.

Governors in several natural resource-dependent states said recently they will have to continue to cut public education funding because prices for oil and coal have not rebounded.

These tools encourage school administrators to gather as much information as possible about the students who will be entering kindergarten and the early-learning offerings in their communities.

Governors in several natural resource-dependent states said recently they will have to continue to cut public education funding because prices for oil and coal have not rebounded.

Resource Mobilization (RM) has replaced the term fundraising as it expanded to account for not only funds but also human resources, goods and services. It is a fundamental component of [...]

Informal Seminar: Human resources policies - Invitation for all Permanent Representatives

 Friday, 12 October 2018 - 15.00 to 17.30 (Green Room)

Ahead of the Food Systems Summit, join the Publications team to find out more about where to find FAO publications, the different formats available, how you can re-use the [...]

Ahead of the Food Systems Summit, join the Publications team to find out more about where to find FAO publications, the different formats available, how you can re-use the [...]

Ahead of the Food Systems Summit, join the Publications team to find out more about where to find FAO publications, the different formats available, how you can re-use the [...]

26 October 2022, 09.00-16.00 (CEST)

Water is a fundamental resource enabling the production of over 95% of food on land as well the progress of all sustainable development goals [...]

The agenda for Natural Resources Committee on 2019-10-09 7:00 PM dated Wednesday, 09 October 2019 has been archived. Access it here:
https://oregon-city.granicus.com/MediaPlayer.php?view_id=4&clip_id=2328 Download File

The agenda for Natural Resources Committee on 2019-11-13 7:00 PM dated Wednesday, 13 November 2019 has been archived. Access it here:
https://oregon-city.granicus.com/MediaPlayer.php?view_id=4&clip_id=2341 Download File

The agenda for Natural Resources Committee on 2019-12-11 7:00 PM dated Wednesday, 11 December 2019 has been archived. Access it here:
https://oregon-city.granicus.com/MediaPlayer.php?view_id=4&clip_id=2359 Download File

The agenda for Natural Resources Committee on 2020-01-08 7:00 PM dated Wednesday, 08 January 2020 has been archived. Access it here:
https://oregon-city.granicus.com/MediaPlayer.php?view_id=4&clip_id=2376 Download File

The agenda for Natural Resources Committee on 2020-03-11 7:00 PM - REVISED dated Wednesday, 11 March 2020 has been archived. Access it here:
https://oregon-city.granicus.com/MediaPlayer.php?view_id=4&clip_id=2404 Download File

To help ease the transition to remote instruction, educators have launched virtual professional learning communities to share resources, ask questions, and give advice.

Penn State is launching a new Employee Resource Group (ERG) for employees who serve as caregivers for other individuals in their lives, including family members such as elders or children of any age who are unwell, or have special needs or disabilities. The new ERG, called Penn State Cares and is open to employees at all campuses, seeks to create a workplace where caregivers can support each other, use and expand existing university resources, and enable employees, who are caregivers, to thrive and grow.

Nearly 30 disability rights and education advocacy organizations have launched a new resource hub and online network designed to help special educators during the coronavirus crisis.

Participants experience a special outreach, Retro-Extreme, in France where they rely on God alone for daily food, housing and ministry opportunities.

September 10 is World Suicide Prevention Day, September is Suicide Prevention and Awareness Month WILMINGTON – In recognition of World Suicide Prevention Day, the Delaware Children’s Department is raising awareness of suicide warning signs and helpful resources, especially during this unprecedented global pandemic. “COVID-19 has magnified the many stressors families grapple with daily, from financial stress […]

WILMINGTON –The Delaware Children’s Department (DSCYF) is sharing mental health and resiliency resources to help families nurture hope during the holiday season and beyond. The COVID-19 pandemic has changed our way of life in Delaware in so many ways, from causing financial strains to impacting our mental health. Even in times of great struggles, however, […]

Free one-on-one counseling and information available to residents; Bureau earns federal grant The Delaware Medicare Assistance Bureau (DMAB), a division of the Delaware Department of Insurance, is encouraging residents to get ready for Medicare Open Enrollment. DMAB, which provides free, one-on-one Medicare counseling, offers a myriad of virtual appointment options for residents, as well as […]

The State of Delaware and E. I. du Pont de Nemours and Company, The Chemours Company, DuPont de Nemours, Inc. and Corteva, Inc, (the “Companies”), businesses with a long history of operations within the State, today announced a settlement agreement designed to benefit Delaware’s natural resources and the people of the State of Delaware now, […]

Attorney General seeks damages, including costs necessary to restore impacted natural resources and funding for State-run public health programs. Attorney General Kathleen Jennings announced that the Department of Justice has filed a lawsuit to hold numerous companies accountable for contaminating Delaware’s natural resources with per- and poly-fluoroalkyl substances (PFAS) traceable to the use and disposal […]

Wilmington, DE. March 21, 2019–Attention educators, parents and employers! The Delaware Department of Labor’s affiliate website, the Delaware Career Resource Network (DCRN), provides information for educators, students and families to learn about careers through activities, handouts, resources, book suggestions, and web links they have placed on the site. It’s a great resource for Take Your […]

DOVER, DE (Oct. 6, 2022) ­– The Delaware Division of Public Health (DPH) has created new resources and a new webinar specifically for pharmacists as part of its ongoing work to reduce substance use disorder.  DPH has worked with partners in the medical community to develop Delaware-specific, evidence-based education materials, aiming to reduce the risk of […]

New campaign underway to highlight support, services available to First State caregivers NEW CASTLE, Del. (Jan. 30, 2023) — The Delaware Department of Health and Social Services (DHSS) has launched a new campaign designed to raise awareness around the many resources available to those who care for and support an older adult or someone living […]

To aid in the ongoing recovery process, the Delaware Emergency Management Agency (DEMA) is announcing the following resources and assistance available to those affected by the recent deadly tornado in Sussex County on April 1.

DNREC encourages families with children 4 to 7 to enjoy exciting “Small Fry Adventures,” a free program about tidal salt marsh and the critters that live there, being held this summer at the Aquatic Resources Education Center near Smyrna.

On August 11, 2011 Governor Jack Markell signed House Bill 123, which proclaimed the month of October to be Disability History and Awareness Month in Delaware.  The bill encourages all schools during the month of October to provide instruction and events focusing on disability history, individuals with disabilities and the disability rights movement.  The Governor’s […]

NA

[DA] Note to editors: Please find attached soundbite by Ian Cameron MP.

Hi

In the environment I'm currently working, axes are shown for schematic, symbol, and layout views.For schematics and symbols, I'd prefer a dim gray, such that the axes are just visible but not dominant. For the layout, I'd prefer a brighter color. Is there a way to realize this? So far when I change the color of the 'axis' layer in the display resource editor, the axes in all three views get changed together:

Thanks very much for your input!

Ogun State Governor, Dapo Abiodun, on Tuesday, said his administration is committed to pursuing fiscal responsibility, through public financial management reforms. This, he said, is to build strong institutions that will promote accountability and transparency. Abiodun made the commitment in Abeokuta during the Treasury Board Meeting on Year 2025-2027 Medium Term Expenditure Framework and the

ADB has a vacancy for the position of (Associate) Human Resource Officer in the Budget, People, and Management Systems Department. The deadline for submitting applications is on 20-NOV-2024.

Retrotransposable elements (RTEs) are common mobile genetic elements comprising ~42% of the human genome. RTEs play critical roles in gene regulation and function, but how they are specifically involved in complex diseases is largely unknown. Here, we investigate the cellular heterogeneity of RTEs using 12 single-cell transcriptome profiles covering three neurodegenerative diseases, Alzheimer's disease (AD), Parkinson's disease, and multiple sclerosis. We identify cell type marker RTEs in neurons, astrocytes, oligodendrocytes, and oligodendrocyte precursor cells that are related to these diseases. The differential expression analysis reveals the landscape of dysregulated RTE expression, especially L1s, in excitatory neurons of multiple neurodegenerative diseases. Machine learning algorithms for predicting cell disease stage using a combination of RTE and gene expression features suggests dynamic regulation of RTEs in AD. Furthermore, we construct a single-cell atlas of retrotransposable elements in neurodegenerative disease (scARE) using these data sets and features. scARE has six feature analysis modules to explore RTE dynamics in a user-defined condition. To our knowledge, scARE represents the first systematic investigation of RTE dynamics at the single-cell level within the context of neurodegenerative diseases.

PWAS (proteome-wide association study) is an innovative genetic association approach that complements widely used methods like GWAS (genome-wide association study). The PWAS approach involves consecutive phases. Initially, machine learning modeling and probabilistic considerations quantify the impact of genetic variants on protein-coding genes’ biochemical functions. Secondly, for each individual, aggregating the variants per gene determines a gene-damaging score. Finally, standard statistical tests are activated in the case-control setting to yield statistically significant genes per phenotype. The PWAS Hub offers a user-friendly interface for an in-depth exploration of gene–disease associations from the UK Biobank (UKB). Results from PWAS cover 99 common diseases and conditions, each with over 10,000 diagnosed individuals per phenotype. Users can explore genes associated with these diseases, with separate analyses conducted for males and females. For each phenotype, the analyses account for sex-based genetic effects, inheritance modes (dominant and recessive), and the pleiotropic nature of associated genes. The PWAS Hub showcases its usefulness for asthma by navigating through proteomic-genetic analyses. Inspecting PWAS asthma-listed genes (a total of 27) provide insights into the underlying cellular and molecular mechanisms. Comparison of PWAS-statistically significant genes for common diseases to the Open Targets benchmark shows partial but significant overlap in gene associations for most phenotypes. Graphical tools facilitate comparing genetic effects between PWAS and coding GWAS results, aiding in understanding the sex-specific genetic impact on common diseases. This adaptable platform is attractive to clinicians, researchers, and individuals interested in delving into gene–disease associations and sex-specific genetic effects.