Dataset Information

Isobaric labeling strategy utilizing 4-plex N, N-dimethyl leucine (DiLeu) tags reveals proteomic changes induced by chemotherapy-related neurotoxicity in cerebrospinal fluid of children

ABSTRACT: Using mass spectrometry for protein identification and quantification in cerebrospinal fluid (CSF) is at the forefront of research efforts to explore the pathophysiology biomarkers for the early diagnosis and prognosis of neurologic disorders. Here we implemented 4-plex N, N-dimethyl leucine (DiLeu) isobaric labeling reagents in a longitudinal study to quantify CSF proteins from children with B-cell acute lymphoblastic leukemia (B-cell ALL) undergoing chemotherapy. Results from this study identified differentially expressed proteins in CSF samples collected from week 5, week 10-14 and week 24-28 compared with samples before Chemo treatment. 84 proteins were significantly altered while Gene Ontology analysis revealed their involvement in various biological processes associated with neurologic disorders. Results from this study will be helpful for monitoring central nervous system (CNS)-specific proteins and developing preventive strategies for CNS injury in response to Chemo.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cerebrospinal Fluid

SUBMITTER: Qinying Yu

LAB HEAD: Lingjun Li

PROVIDER: PXD017415 | Pride | 2020-07-02

REPOSITORIES: Pride

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Publications

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.

Yu Qinying Q Zhong Xiaofang X Chen Bingming B Feng Yu Y Ma Min M Diamond Carol A CA Voeller Julie S JS Kim Miriam M DeSantes Kenneth B KB Capitini Christian M CM Patel Neha J NJ Hoover-Regan Margo L ML Burke Michael J MJ Janko Kimberly K Puccetti Diane M DM Ikonomidou Chrysanthy C Li Lingjun L

Journal of proteome research 20200527 7

The use of mass spectrometry for protein identification and quantification in cerebrospinal fluid (CSF) is at the forefront of research efforts to identify and explore biomarkers for the early diagnosis and prognosis of neurologic disorders. Here we implemented a 4-plex N,N-dimethyl leucine (DiLeu) isobaric labeling strategy in a longitudinal study aiming to investigate protein dynamics in children with B-cell acute lymphoblastic leukemia (B-cell ALL) undergoing chemotherapy. The t ...[more]

PMID: 32396724

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Project description:Neurologic manifestations are among the most frequently reported complications of COVID-19. However, given the paucity of tissue samples and highly infectious nature of the etiologic agent of COVID-19, we have limited information to understand the neuropathogenesis of COVID-19. Therefore to better understand the impact of COVID-19 in brain, we employed mass-spectrometry-based proteomics using data-independent acquisition mode (DIA) to investigate cerebrospinal fluid (CSF) proteins collected from two different non-human primates, Rhesus Macaque and African Green Monkeys for the neurologic effects of the infection. These monkeys exhibited minimal to mild pulmonary pathology but moderate to severe CNS pathology. Our results indicate that CSF proteome changes after infection resolution correspond with bronchial virus abundance during early infection and revealed substantial differences between the infected NHPs and their age-matched uninfected controls, suggesting these differences could reflect altered secretion of CNS factors in response to SARS-CoV-2-induced neuropathology. We also observed the infected animals to exhibit much scattered data distributions as compared to the tightly clustered corresponding controls which suggest the heterogeneity of the CSF proteome change and the host response to the viral infection. In addition, dysregulated CSF proteins were preferentially enriched in functional pathways associated with progressive neurodegenerative disorders, hemostasis and innate immune responses that could influence neuroinflammatory responses following COVID-19. Mapping dysregulated proteins to the Human Brain Protein Atlas found that these proteins tended to be enriched in brain regions that exhibit more frequent injury following COVID-19. It therefore appears reasonable to speculate that such CSF protein changes could serve as signatures for neurologic injury, identify important regulatory pathways in this process, and potentially reveal therapeutic targets to prevent or attenuate the development of neurologic injuries following COVID-19.

Dataset Information

Isobaric labeling strategy utilizing 4-plex N, N-dimethyl leucine (DiLeu) tags reveals proteomic changes induced by chemotherapy-related neurotoxicity in cerebrospinal fluid of children

Publications

Isobaric Labeling Strategy Utilizing 4-Plex <i>N</i>,<i>N</i>-Dimethyl Leucine (DiLeu) Tags Reveals Proteomic Changes Induced by Chemotherapy in Cerebrospinal Fluid of Children with B-Cell Acute Lymphoblastic Leukemia.

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