Cascadia is a mass spectrometry-based de novo sequencing model that uses a transformer architecture to handle data-independent acquisition data and achieves substantially improved performance across a...

A theoretical foundation for entrapment methods is presented, along with a method that enables more accurate evaluation of false discovery rate (FDR) control in proteomics mass spectrometry analysis p...

Mass spectrometry is the dominant technology in the field of proteomics, enabling high-throughput analysis of the protein content of complex biological samples. Due to the complexity of the instrument...

Nuclear DNA is organized into a compact three-dimensional (3D) structure that impacts critical cellular processes. High-throughput chromosome conformation capture (Hi-C) is the most widely used method...

AbstractMotivation. The Basic Local Alignment Search Tool, BLAST, is an indispensable tool for genomic research. BLAST established itself as the canonical

Quantitative analysis of proteomics data frequently employs peptide-identity-propagation (PIP) — also known as match-between-runs (MBR) — to increase the number of peptides quantified in a given LC-MS/MS experiment. PIP can routinely account for up to 40% of all quantitative results, with that proportion rising as high as 75% in single-cell proteomics. Therefore, a significant concern for any PIP method is the possibility of false discoveries: errors that result in peptides being quantified incorrectly. Although several tools for label-free quantification (LFQ) claim to control the false discovery rate (FDR) of PIP, these claims cannot be validated as there is currently no accepted method to assess the accuracy of the stated FDR. We present a method for FDR control of PIP, called “PIP-ECHO” (PIP Error Control via Hybrid cOmpetition) and devise a rigorous protocol for evaluating FDR control of any PIP method. Using three different datasets, we evaluate PIP-ECHO alongside the PIP procedures implemented by FlashLFQ, IonQuant, and MaxQuant. These analyses show that PIP-ECHO can accurately control the FDR of PIP at 1% across multiple datasets. Only PIP-ECHO was able to control the FDR in data with injected sample size equivalent to a single-cell dataset. The three other methods fail to control the FDR at 1%, yielding false discovery proportions ranging from 2–6%. We demonstrate the practical implications of this work by performing differential expression analyses on spike-in datasets, where different known amounts of yeast or E. coli peptides are added to a constant background of HeLa cell lysate peptides. In this setting, PIP-ECHO increases both the accuracy and sensitivity of differential expression analysis: our implementation of PIP-ECHO within FlashLFQ enables the detection of 53% more differentially abundant proteins than MaxQuant and 146% more than IonQuant in the spike-in dataset. ### Competing Interest Statement The authors have declared no competing interest.

Ultra-fast label-free quantification algorithm for mass-spectrometry proteomics - smith-chem-wisc/FlashLFQ

Quantitative analysis of proteomics data frequently employs peptide-identity-propagation (PIP) — also known as match-between-runs (MBR) — to increase the number of peptides quantified in a given LC-MS...

In any machine learning study, high quality data for training and validating the model is critical. This paper describes the result of an iterative process of data wrangling and quality control, which...

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