Viewing posts tagged 2020

LipidGenie, a genome-guided lipid identification tool

Despite the crucial roles of lipids in metabolism, we are still in the early stages of annotating lipid species and their genetic basis. To help in this work, a team of researchers led by Vanessa Linke recently developed LipidGenie, an interactive, query-able resource for lipid identification. The research team used high-resolution liquid chromatography–tandem mass spectrometry to quantify 3,283 molecular features from the liver and plasma of outbred mice. These features were then mapped to 5,622 lipid quantitative trait loci, compiled and cross-referenced to the human genome.

Download the software and read the manuscript.

Relish protein level affects secondary traumatic brain injuries

Brain trauma is caused by both primary and secondary injuries. Primary injuries result from the physical damage to the brain, and secondary injuries from the bodies’ responses to those injuries. A recent publication in Genetics by Swanson et al. describes using mass spectrometry to investigate secondary injuries in the Relish (Rel) protein level in fly heads after a primary brain injury. They found changes in Rel levels were necessary for secondary traumatic brain injuries to occur.

Fast, unbiased proteome quantification without LC

Liquid chromatography–mass spectrometry (LC–MS) delivers sensitive peptide analysis for proteomics but requires extensive analysis time, reducing productivity. A recent paper by Meyer et al. titled “Quantitative shotgun proteome analysis by direct infusion” demonstrated that gas-phase peptide separation using direct infusion–shotgun proteome analysis enabled fast, unbiased proteome quantification without LC, and offered an approach to boost throughput, critical to studies that require analysis of thousands of proteomes.

Gut microbiome may play a role in brain functions and behaviors

Gut microbiota can regulate host physiological and pathological status through gut–brain communications or pathways. However, the impact of the gut microbiome on the proteins involved in regulating brain functions and behaviors is still not clearly understood. In a recent publication by Liu et al., the author describes a combined label-free and 10-plex DiLeu-based quantitative method that enabled a comprehensive profiling of gut microbiome that induced dynamic changes, suggesting that the gut microbiome might mediate a range of behavioral changes, brain development, and learning and memory through these neuropeptides and proteins.

Liu R et al. Integrated Label-Free and 10-plex DiLeu Isobaric Tag Quantitative Methods for Profiling Changes in the Mouse Hypothalamic Neuropeptidome and Proteome: Assessment of the Impact of the Gut Microbiome. Analytical Chemistry.

DiLeu tagging for protein and phosphorylation quantification in parallel

For the first time, DiLeu tagging has been implemented for protein and phosphorylation quantification in parallel. This process was described in a recent publication by Zhong et al titled Highly multiplexed quantitative proteomic and phosphoproteomic analyses in vascular smooth muscle cell dedifferentiation.

The research team developed a strategy that used 12-plex N,N-dimethyl leucine (DiLeu) isobaric tags together with the DiLeu software tool to globally assess protein expression and phosphorylation changes in smooth muscle cells (SMCs) treated with TGFβ/Smad3 and/or SDF-1α (stromal cell-derived factor).

The goal of this work was to develop insights into the mechanisms of TGFβ regulated SMC dedifferentiation, as well as effective therapeutics for vascular disease.

Creating efficient and effective peptide fragmentation in tandem MS (MS/MS)

Photoactivation and photodissociation have long proven to be useful tools in tandem mass spectrometry, but implementation often involves cumbersome and potentially dangerous configurations. To remedy this problem, a fiber-optic cable was coupled to an infrared (IR) laser on a mass spectrometer. These advances allow for a more robust, straightforward, and safe instrumentation platform, permitting implementation of AI-ETD and IRMPD on commercial mass spectrometers and broadening the accessibility of these techniques.

This research is described in a recent Analytical Chemistry publication by Trent Peters-Clarke titled Optical Fiber-Enabled Photoactivation of Peptides and Proteins.


Li lab project uses DiLeu isobaric labeling to monitor neurotoxicity in chemotherapy in children

A new project by the Lingjun Li lab explores the use of the 4-plex N,N-dimethyl leucine (DiLeu) isobaric labeling strategy for protein identification and quantification in cerebrospinal fluid in children undergoing chemotherapy. The results from this and future studies will provide a means to monitor neurotoxicity and develop strategies to prevent central nervous system injury in response to chemotherapy in children.

The publication is Isobaric labeling strategy utilizing 4-plex N,N-dimethyl leucine (DiLeu) tags reveals proteomic changes induced by chemotherapy in cerebrospinal fluid of children with B-cell acute lymphoblastic leukemia from the Journal of Proteome Research.

DiLeu isobaric tags achieves 21-plex quantification

Isobaric tags enable multiplexed quantitative analysis of many biological samples in a single LC-MS/MS experiment. As a cost-effective alternative to expensive commercial isobaric tagging reagents, the lab of Lingjun Li has developed their own custom “DiLeu” isobaric tags for quantitative proteomics. In this paper, Dustin Frost showcases a new generation of DiLeu tags that achieves 21-plex quantification in high-resolution HCD MS/MS spectra.

21-plex DiLeu Isobaric Tags for High-throughput Quantitative Proteomics. Analytical Chemistry.

Li lab collaboration yields insights into spinal cord stimulation for pain relief

A recent publication by Tilley et al titled Proteomic modulation in the dorsal spinal cord following spinal cord stimulation therapy in an in vivo neuropathic pain model, explores how Spinal cord stimulation (SCS) can provide relief for patients suffering from chronic pain, with less dependence on electrical interference. Recent evidence has been growing regarding molecular changes that are induced by SCS as being a key player in reversing the pain process. In this paper the effect of SCS on altering protein expression in spinal cord tissue using a proteomic analysis approach are observed.

Multi-Omics of COVID-19 Collaboration with Albany Medical College

A collaboration with the lab of Dr. Ariel Jaitovich at Albany Medical College studied a Large-scale Multi-omic Analysis of COVID-19 Severity (in preprint). Over 17,000 transcripts, proteins, metabolites, and lipids were quantified and associated with clinical outcomes in a curated relational database, uniquely enabling systems analysis and cross-ome correlations to molecules and patient prognoses. A web-based tool (covid-omics.app) enables interactive exploration and illustrates its utility through a comparative analysis with published data and a machine learning prediction of COVID-19 severity.