Project description:This is a dataset used for the orchestration of molecular networking which led the discovery of polyacetylated 18-norspirostanol saponins from Trillium tschonoskii.
Project description:Mass spectrometry is the current technique of choice in studying drug metabolism. High-resolution mass spectrometry (HR-MS) in combination with fragment analysis (MS/MS) has the potential to contribute to rapid advances in this field. However, the data emerging from such fragmentation spectra pose challenges to downstream analysis, given their complexity and size. Here we apply a molecular networking approach to seek drugs and their metabolites, in fragmentation spectra from urine derived from a cohort of 26 patients on antihypertensive therapy. In total, 165 separate drug metabolites were found and structurally annotated (17 by spectral matching and 122 by classification based on a clustered fragmentation pattern). The clusters could be traced to 13 drugs including the known antihypertensives verapamil, losartan and amlopidine. The molecular networking approach also generated networks of endogenous metabolites, including carnitine derivatives, and conjugates containing glutamine, glutamate and trigonelline. The approach offers unprecedented capability in the untargeted identification of drugs and their metabolites at the population level and has great potential to contribute to understanding stratified responses to drugs where differences in drug metabolism may determine treatment outcome. Keywords: Antihypertensive drugs, Drug metabolism, Fragmentation, High-resolution mass spectrometry, Metabolomics, Urine.
Project description:Example dataset for Methods in Molecular Biology Chapter - Feature Based Molecular Networking for Metabolite Annotation. This dataset includes the LC-MS/MS raw data (Bruker .d file format and centroided mzXML file format), metadata table used for the ste-by-step instructions, a batch file for MZmine2 data processing, and all resulting files from the MZmine2 and GNPS processing.
Project description:Despite the overwhelming information about sRNAs, one of the biggest challenges in the sRNA field is characterizing sRNA targetomes. Thus, we develop a novel method to identify RNAs that interact with a specific sRNA, regardless of the type of regulation (positive or negative) or targets (mRNA, tRNA, sRNA). This method is called MAPS: MS2 affinity purification coupled with RNA sequencing. As proof of principle, we identified RNAs bound to RybB, a well-characterized E. coli sRNA. Identification of RNAs co-purified with MS2-RybB in a rne131 ΔrybB strain. RybB (without MS2) was used as control
Project description:Despite the overwhelming information about sRNAs, one of the biggest challenges in the sRNA field is characterizing sRNA targetomes. Thus, we develop a novel method to identify RNAs that interact with a specific sRNA, regardless of the type of regulation (positive or negative) or targets (mRNA, tRNA, sRNA). This method is called MAPS: MS2 affinity purification coupled with RNA sequencing. As proof of principle, we identified RNAs bound to RyhB, a well-characterized E. coli sRNA. Identification of RNAs co-purified with MS2-RyhB in a rne131 ?ryhB strain. RyhB (without MS2) was used as control
Project description:This study intends to explore the clinicopathological characteristics and survival prognosis of locally recurrent colorectal cancer patients with different treatment modes by retrospectively analyzing the medical records of locally recurrent colorectal cancer patients who received hospitalization in our center. Transcriptome sequencing and public databases were used to screen for molecular markers related to locally recurrent colorectal cancer and to explore molecular markers’ regulatory role in the progression of locally recurrent colorectal cancer.
Project description:The Myc/Max heterodimer has crucial roles in normal cellular processes such as cell proliferation, metabolism, apoptosis, and differentiation, but its activity is often deregulated in a majority of human cancers. In an effort to explore alternative modes of Myc perturbation, we identified KI-MS2-008 as a small molecule that binds Max and modulates Myc-driven transcription, and in some cellular contexts, KI-MS2-008 treatment leads to a decrease in c-Myc protein levels. As the Myc/Max heterodimer controls many cellular processes, we expected that treatment with this small molecule would cause changes in the transcriptome. We found that treatment with 10 µM KI-MS2-008 resulted in global alterations in the transcriptome, mimicking direct Myc inactivation with doxycycline in P493-6, a B cell line with a Tet-Off system for c-Myc expression. We also discovered enrichment of various Myc target gene sets in the genes downregulated in response to KI-MS2-008 treatment in P493-6 cells. This trend was also observed in ST486 cells, but not in P3HR1 cells, which were chosen as non-engineered B cell lines that were sensitive and insensitive, respectively, toward KI-MS2-008 in cell viability assays.
Project description:Molecular networking has become a key method to visualize and annotate the chemical space in non-targeted mass spectrometry data. We present feature-based molecular networking (FBMN) as an analysis method in the Global Natural Products Social Molecular Networking (GNPS) infrastructure that builds on chromatographic feature detection and alignment tools. FBMN enables quantitative analysis and resolution of isomers, including from ion mobility spectrometry.
Project description:MS2 experiments with 3 CE: 10, 20, 30 eV for schizokinen derivatives, schizokinen, schizokinen A, N-deoxy-schizokinen and N-deoxy-schizokinen A