PXD024651

PXD024651 is an original dataset announced via ProteomeXchange.

Title	Alternative LC-MS/MS Platforms and Data Acquisition Strategies for Proteomic Genotyping
Description	Protein is a major component of all biological evidence. Proteomic genotyping is the use of genetically variant peptides that contain single amino acid polymorphisms to infer the genotype of matching non-synonymous single nucleotide polymorphisms for the individual who originated the protein sample. This can be used to statistically associate an individual to forensic evidence. The utility of the inferred genotype increases as the detection of genetically variant peptides increases and as the technology is transferred to mass spectrometry platforms available to forensic practitioners. Digests of single (2 cm) human hair shafts from three European and two African subjects were analyzed using data dependent acquisition on a Q-Exactive™ Plus Hybrid Quadrupole-Orbitrap™ system, data independent acquisition and a variant of parallel reaction monitoring on a Orbitrap Fusion™ Lumos™ Tribrid™ system, and multiple reaction monitoring on an Agilent 6495 triple quadrupole system. In our hands, average genetically variant peptide detection from a selected 24 genetically variant peptide panel increased from 6.5 ± 1.1 and 3.1 ± 0.8 using data dependent and independent acquisition to 9.5 ± 0.7 and 11.7 ± 1.7 using parallel reaction and multiple reaction monitoring (p < 0.05). Targeted methods of analysis resulted in a 1.3-fold to 1.6-fold increase in detection sensitivity. This increase in biomarker detection has a functional impact on the statistical association of a protein sample and an individual. Increased biomarker sensitivity, using Markov Chain Monte Carlo modeling, produced a median estimated random match probability of over 1 in 10 billion to 1 in 10 trillion from a single hair using targeted proteomics. Detected genetically variant peptides were validated by the inclusion of stable isotope labeled peptides in each sample, which served also as a detection trigger. This research accomplishes two aims: the demonstration of utility for alternative analytical platforms in proteomic genotyping, and the establishment of validation methods for the evaluation of inferred genotypes by forensic practitioners.
HostingRepository	PanoramaPublic
AnnounceDate	2021-09-10
AnnouncementXML	Submission_2021-09-10_13:56:34.292.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Glendon Parker
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	Acetyl; Carbamidomethyl; Label:13C(6)15N(2); Label:13C(6)15N(4)
Instrument	Q Exactive Plus; Orbitrap Fusion Lumos; 6495A Triple Quadrupole LC/MS

Revision	Datetime	Status	ChangeLog Entry
0	2021-03-10 14:15:27	ID requested
⏵ 1	2021-09-10 13:56:34	announced

Goecker ZC, Legg KM, Salemi MR, Herren AW, Phinney BS, McKiernan HE, Parker GJ, Alternative LC-MS/MS Platforms and Data Acquisition Strategies for Proteomic Genotyping of Human Hair Shafts. J Proteome Res, 20(10):4655-4666(2021) [pubmed]

submitter keyword: Genetically Variant Peptide, Hair, Forensic

Glendon Parker
contact affiliation	University of California, Davis
contact email	gjparker@ucdavis.edu
lab head
Glendon Parker
contact affiliation	University of California, Davis
contact email	gjparker@ucdavis.edu
dataset submitter

Panorama Public dataset URI