Poster Presentation 27th Annual Lorne Proteomics Symposium 2022

Automated workflows for DIA data using DIA-NN on the PaSER platform (#171)

Christopher Adams 1 , Robin Park 1 , Sven Brehmer 2 , Adam Rainczuk 3 , Tharan Srikumar 1 , Nagarjuna Nagaraj 2
  1. Bruker Daltonics, San Jose, CA, USA
  2. Bruker Daltonics, Bremen, Germany
  3. Bruker Pty Ltd, Preston, Australia

Data independent acquisition has become the go to method for deep and quantitative proteomic analysis, given the ability to sample large m/z windows in a reproducible and non-stochastic manner. Using a method termed dia-PASEF on a TIMS enabled Q-TOF lends additional advantages in both duty cycle and selectivity using the ion mobility space. Dia-PASEF allows for deep proteomes in short gradient times (<20 min.) and therefore 100’s of LCMS runs can be generated in short times. Data analysis in a streamlined automated fashion expedites the time from experiments to discovery. DIA-NN is a novel software package that uses neural networks providing best-in-class DIA output. Here we integrate DIA-NN onto the PaSER platform for a streamlined workflow for the analysis of many samples in a short analysis time with no file transfer or data migration.

Methods: A timsTOF Pro using variable CE’s and mobility windows in gradients ranging from 5 min. to 90 min. were used. DIA-NN was modified to become CCS-enabled and process data in the most expedient fashion. The PaSER GUI was designed such that first-pass analysis is predefined automatically triggering quantitative analysis.  Retrospectively, match-between-runs (MBR) analysis can be triggered on the whole project or subset of user defined experiments. 

Preliminary Data: Human, Yeast and E. coli (HYE) digested mixtures at different but known ratios with injection loads from 50ng to 600ng were run at different gradient lengths in replicate resulting in >2500 proteins at short gradients to >9000 proteins identified and quantified at longer gradients. Quantitative accuracy was shown to be <20% CV. Using the DIA-NN as integrated into PaSER creates a seamless approach to dia-PASEF analysis.

Novel Aspect: Automated workflows for dia-PASEF using DIA-NN on PaSER streamlines experiments to results