CIDer: a statistical framework for interpreting differences in CID and HCD fragmentation
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Orbitrap Fusion Lumos
ORGANISM(S): Homo Sapiens (ncbitaxon:9606)
SUBMITTER: 
Danielle Swaney Brian Searle
PROVIDER: MSV000086855 | MassIVE | Fri Feb 12 05:02:00 GMT 2021
SECONDARY ACCESSION(S): PXD024157
REPOSITORIES: MassIVE
Similar Datasets
Project description:Library searching is a powerful technique for detecting peptides using either data independent or data dependent acquisition. While both large-scale spectrum library curators and deep learning prediction approaches have focused on beam-type CID fragmentation (HCD), resonance CID fragmentation remains a popular technique. Here we demonstrate an approach to model the differences between HCD and CID spectra, and present a software tool, CIDer, for converting libraries between the two fragmentation methods. We demonstrate that just using a combination of simple linear models and basic principles of peptide fragmentation, we can explain up to 43% of the variation between ions fragmented by HCD and CID across an array of collision energy settings. We further show that in some circumstances, searching converted CID libraries can detect more peptides than searching existing CID libraries or libraries of machine learning predictions from FASTA databases. These results suggest that leveraging information in existing libraries by converting between HCD and CID libraries may be an effective interim solution while large-scale CID libraries are being developed.
| S-EPMC8256874 | biostudies-literature
Project description:ADP-ribosylation is a posttranslational modification whose HCD products are dominated by complete or partial modification losses, complicating peptide sequencing and acceptor site localization efforts. We tested whether in-source CID performed on a quadrupole Orbitrap could convert ADPr to the smaller phosphoribose-H2O derivative to facilitate HCD-dependent peptide sequencing. Human macrophage like cell line THP-1-derived ADP-ribosyl (ADPr) peptides were analyzed on a quadrupole Orbitrap. We monitored the interconversion of ADPr (+541.061 Da) to phosphoribosyl-H2O (+193.997 Da) peptides while varying the source and high-field asymmetric waveform ion mobility mass spectrometry (FAIMS) compensation voltages. Xcorr and ptmRS were used to evaluate peptide sequencing and acceptor site confidence, respectively. In-source CID-HCD-derived phosphoribosyl-H2O acceptor sites were compared to those determined by EThcD, performed on a quadrupole ion trap Orbitrap. Interconversion of ADPr peptides to their phosphoribosyl-H2O derivatives increased with increasing source voltage (up to 50V), as judged by monitoring the corresponding modification loss ([adenosine monophosphate/AMP]+) and the number of identified phosphoribosyl-H2O peptide identifications. The average Xcorr increased from 1.36 (ADPr) to 2.26 (phosphoribosyl-H2O), similar to that achieved with EThcD for ADPr peptides (2.29). The number of high-confidence acceptor sites (>95%) also increased, from 31% (ADPr) to 70% (phosphoribosyl-H2O), which was comparable to EThcD (70%). In-source CID converts ADP-ribosyl to phosphoribosyl-H2O peptides that are more amenable to HCD-dependent peptide sequencing, providing an alternative method for acceptor site determination when ETD-based methods are not available.
2024-12-05 | PXD055586 | Pride
Project description:Citrullination is a protein PTM of arginine residues catalyzed by peptidylarginine deiminase. Protein citrullination has been detected in the CNS and associated with a number of neurological diseases. However, identifying citrullinated proteins from complex mixtures and pinpointing citrullinated residues have been limited. Using RP LC and high-resolution MS, this study determined in vitro citrullination sites of glial fibrillary acid protein (GFAP), neurogranin (NRGN/RC3), and myelin basic protein (MBP) and in vivo sites in brain protein extract. Human GFAP has five endogenous citrullination sites, R30, R36, R270, R406, and R416, and MBP has 14 in vivo citrullination sites. Human NRGN/RC3 was found citrullinated at residue R68. The sequence of citrullinated peptides and citrullination sites were confirmed from peptides identified in trypsin, Lys-C, and Glu-C digests. The relative ratio of citrullination was estimated by simultaneous identification of citrullinated and unmodified peptides from Alzheimer's and control brain samples. The site occupancy of citrullination at the residue R68 of NRGN ranged from 1.6 to 9.5%. Compared to CID, higher-energy collisional dissociation (HCD) mainly produced protein backbone fragmentation for citrullinated peptides. CID-triggered HCD fragmentation is an optimal approach for the identification of citrullinated peptides in complex protein digests.
| S-EPMC4864592 | biostudies-literature
Project description:CID 70698683 is a novel broad-spectrum antiviral compound. To understand the broad-spectrum antiviral mechanism, the cellular gene expression changes by the treatment of CID70698683 was measured. HEp-2 cells grown in 6-well plates were treated with 5 microM of CID 70698683 for overnight and the cellular RNA was extracted (Treatment group). For control, DMSO was used instead of CID 70698683 (final concentration of 0.25%). Three replicates per group used.
2015-11-25 | E-GEOD-72167 | biostudies-arrayexpress
Project description:The centromere-specific Histone H3-variant CENH3 (also known as CENP-A) is considered to be an epigenetic mark for establishment and propagation of centromere identity. Pulse-induction of CENH3 (Drosophila CID) in Schneider S2 cells incorporates into noncentromeric regions and generates CID islands that resist clearing from chromosome arms for multiple cell generations. We demonstrate that CID islands represent functional ectopic kinetochores, which are non-randomly distributed on the chromosome and display a preferential localization near telomeres and pericentric heterochromatin in transcriptionally silent, intergenic chromatin domains. Although overexpression of heterochromatin protein 1 (HP1) or increasing Histone acetylation interferes with CID islands formation on a global scale, induction of a locally defined region of synthetic heterochromatin by targeting HP1-LacI fusions to stably integrated Lac Operator arrays produces a proximal hotspot for CID islands formation. These data suggest that the characteristics of regions bordering heterochromatin promote de novo kinetochore assembly and thereby contribute to centromere identity. ArrayExpress Release Date: 2011-07-15 Person Roles: submitter Person Last Name: Diehl Person First Name: Sarah Person Mid Initials: Person Email: diehl@immunbio.mpg.de Person Phone: (+49) 761 5108 795 Person Address: Stuebeweg 51, 79108 Freiburg im Breisgau, Germany Person Affiliation: Max-Planck-Institute for Immunobiology and Epigenetics Person Roles: investigator Person Last Name: Heun Person First Name: Patrick Person Mid Initials: Person Email: heun@immunbio.mpg.de Person Phone: (+49) 761 5108 717 Person Address: Stuebeweg 51, 79108 Freiburg im Breisgau, Germany Person Affiliation: Max-Planck-Institute for Immunobiology and Epigenetics Publication Title: Heterochromatin boundaries are hotspots for de novo kinetochore formation. Publication Author List: Agata Olszak, Dominic van Essen, Antonio J. Pereira, Sarah Diehl, Thomas Manke, Helder Maiato, Simona Saccani and Patrick Heun
2012-01-20 | GSE30997 | GEO
Project description:Compound CID 3538206 inhibits yeast TORC1 activity and functionally mimic rapamycin. We used microarrays to compare the global gene expression with the treatment of CID 3528206 and rapamycin.
2012-05-01 | GSE33320 | GEO
Project description:CID 70698683 is a novel broad-spectrum antiviral compound. To understand the broad-spectrum antiviral mechanism, the cellular gene expression changes by the treatment of CID70698683 was measured.
2015-11-25 | GSE72167 | GEO
Project description:A variety of high-throughput techniques are now available for constructing comprehensive gene regulatory networks in systems biology. In this study, we report a new statistical approach for facilitating in silico inference of regulatory network structure. The new measure of association, coefficient of intrinsic dependence (CID), is model-free and can be applied to both continuous and categorical distributions. When given two variables X and Y, CID answers whether Y is dependent on X by examining the conditional distribution of Y given X. In this paper, we apply CID to analyze the regulatory relationships between transcription factors (TFs) (X) and their downstream genes (Y) based on clinical data. More specifically, we use estrogen receptor alpha (ERalpha) as the variable X, and the analyses are based on 48 clinical breast cancer gene expression arrays (48A). RESULTS: The analytical utility of CID was evaluated in comparison with four commonly used statistical methods, Galton-Pearson's correlation coefficient (GPCC), Student's t-test (STT), coefficient of determination (CoD), and mutual information (MI). When being compared to GPCC, CoD, and MI, CID reveals its preferential ability to discover the regulatory association where distribution of the mRNA expression levels on X and Y does not fit linear models. On the other hand, when CID is used to measure the association of a continuous variable (Y) against a discrete variable (X), it shows similar performance as compared to STT, and appears to outperform CoD and MI. In addition, this study established a two-layer transcriptional regulatory network to exemplify the usage of CID, in combination with GPCC, in deciphering gene networks based on gene expression profiles from patient arrays. CONCLUSION: CID is shown to provide useful information for identifying associations between genes and transcription factors of interest in patient arrays. When coupled with the relationships detected by GPCC, the association predicted by CID are applicable to the construction of transcriptional regulatory networks. This study shows how information from different data sources and learning algorithms can be integrated to investigate whether relevant regulatory mechanisms identified in cell models can also be partially re-identified in clinical samples of breast cancers. AVAILABILITY: the implementation of CID in R codes can be freely downloaded from (http://homepage.ntu.edu.tw/~lyliu/BC/).
2009-07-10 | GSE17041 | GEO
Project description:The centromere-specific Histone H3-variant CENH3 (also known as CENP-A) is considered to be an epigenetic mark for establishment and propagation of centromere identity. Pulse-induction of CENH3 (Drosophila CID) in Schneider S2 cells incorporates into noncentromeric regions and generates CID islands that resist clearing from chromosome arms for multiple cell generations. We demonstrate that CID islands represent functional ectopic kinetochores, which are non-randomly distributed on the chromosome and display a preferential localization near telomeres and pericentric heterochromatin in transcriptionally silent, intergenic chromatin domains. Although overexpression of heterochromatin protein 1 (HP1) or increasing Histone acetylation interferes with CID islands formation on a global scale, induction of a locally defined region of synthetic heterochromatin by targeting HP1-LacI fusions to stably integrated Lac Operator arrays produces a proximal hotspot for CID islands formation. These data suggest that the characteristics of regions bordering heterochromatin promote de novo kinetochore assembly and thereby contribute to centromere identity.
2011-07-15 | E-MTAB-652 | biostudies-arrayexpress