CHIMERYS is an intelligent, AI-powered search algorithm for bottom-up proteomic data analysis. The name "CHIMERYS" originates from its remarkable ability to deconvolute chimeric MS2 spectra, a frequent phenomenon in tandem mass spectrometry, where multiple peptides are co-isolated and co-fragmented due to similar physicochemical properties. CHIMERYS 4 is a spectrum-centric search algorithm and compatible with data-dependent acquisition (DDA),  data-independent acquisition (DIA), and parallel reaction monitoring (PRM) data. 

CHIMERYS leverages the power of accurately predicted peptide properties, which are obtained from the deep-learning framework INFERYS™. CHIMERYS utilizes predicted spectra to best explain the experimental MS2 spectrum with the fewest candidates possible. This way, the algorithm deconvolutes the experimental intensities and derives the contributions for all peptides in the MS2 spectrum. This enables CHIMERYS to identify multiple peptides in chimeric MS2 spectra. The algorithm operates in a spectrum-centric manner and is fully compatible with MS2 spectra from various acquisition methods. 

CHIMERYS 1.0 was introduced in 2022 and released as part of Proteome Discoverer 3.0. CHIMERYS 1.0 is compatible with DDA data only. In 2023, we unveiled CHIMERYS 2.0, which is integrated into Proteome Discoverer 3.1 and supports the analysis of data data-dependent acquisition (DDA), data data-interdependent (DIA), and parallel reaction monitoring (PRM) data, providing you with an unifying data analysis solution for all popular proteomics data acquisition types. This year we have launched CHIMERYS 4 with more supported PTM such as Oxidation, Phosphorylation, Acetylation, Ubiquitination, unmodified Cysteines, and PreOmics iST NHS. Additionally, your DIA data is processing is twice as fast compared to the previous version. All data is subjected to identical and rigorous, spectrum-centric error control. The FDR estimation is stable across all isolation window sizes and enables fair comparisons of DDA and DIA data. 

CHIMERYS 4 is implemented as a subscription-based cloud service. Thermo Fisher Scientific hosts the CHIMERYS service using Amazon Web Services on servers physically located in Ireland. While new servers will be added in other geographies, our European customers will continue to use the servers in Ireland. The CHIMERYS node in Proteome Discoverer extracts the MS/MS spectra from .RAW files and sends them along with a .FASTA file to the service for the search. All communication with the service is encrypted via HTTPS ensuring data security. The data may be queued as it is waiting for other CHIMERYS runs to finish depending on the type of subscription purchased. Once the CHIMERYS analysis is complete, the peptide identifications are securely transmitted back to Proteome Discoverer and the collection of MS/MS spectra and the FASTA file are deleted from the service. It is worth noting that .RAW files and .RAW file metadata are never transmitted to the service, ensuring the privacy and confidentiality of this data. 

We recently uploaded a bioRxiv pre-print describing in detail all the technical foundation as well as numerous applications: Unifying the analysis of bottom-up proteomics data with CHIMERYS. The paper was since handed in for publication after peer review in a high-impact journal. 

CHIMERYS 4 is integrated into Proteome Discoverer 3.2 software. To learn more about licensing and obtain the software, please visit Proteome Discoverer page or get in touch with your local Thermo Scientific sales representative. You can also request a free Proteome Discoverer 3.2 and CHIMERYS 4 demo here.  

You can request a free CHIMERYS 4 demo here or visit the Proteome Discoverer page. We will send you login credentials with 24 hours of CHIMERYS processing time, which roughly translates to 24 hours of LC-MS/MS measurement time. If you need more time, please do not hesitate to reach out to us via info@msaid.de.

Proteome Discoverer 3.2 software comes with a subscription to the CHIMERYS cloud service. There are three subscription tiers available: Lite, Full and Plus. The difference between them is the number of daily compute capacity available on the CHIMERYS cloud service. For a detailed description of the subscription options and licensing information, please visit the Proteome Discoverer page or get in touch with your local Thermo Scientific sales representative.

CHIMERYS 4's capabilities are in part dependent on the capabilities of the deep-learning framework INFERYS™, which predicts peptide properties crucial for reliable peptide identification. CHIMERYS 4 is compatible with Thermo Fisher .RAW files and MS2 spectra derived from Orbitrap™, Ion Trap, or Astral™ mass analyzers. It supports the analysis of DDA, DIA, and PRM data of label-free or Tandem-mass tag™ (TMT6/10/11 and TMTpro based quantification) labeled peptides of length 7 to 30 amino acids. It can handle a multitude of proteolytic enzymes, oxidized methionine and phosphorylated serine, threonine, and tyrosine residues as variable modifications and carbamidomethylated cysteine as a fixed modification. CHIMERYS 4 is not compatible with crosslinked peptides and glycopeptides.  

Configuring a CHIMERYS search within the Proteome Discoverer Software is a simple and user-friendly task. If you'd like a step-by-step visual walkthrough on how to set up a CHIMERYS search job, we've prepared an informative video tutorial that you can access by clicking here.

If you encounter any difficulties or have any questions, our support team is always here to help you. Feel free to reach out for any assistance you may require.

Setting up a CHIMERYS in the Proteome Discoverer Software is a straightforward process that can be completed in two easy steps: Step 1: Download and install the Proteome Discoverer 3.1 software demo. Step 2: Log into the CHIMERYS service using the provided credentials. For detailed guidance on setting up the CHIMERYS demo, you can download the CHIMERYS Demo Installation guide from  here.

Which PTMs can be analyzed with CHIMERYS depends on the capabilities of the deep-learning framework INFERYS™ that predicts peptide properties used for the identification of peptides. Currently, CHIMERYS is compatible with methionine oxidation, phosphorylation, acetylation, ubiquitination, unmodified Cysteines, and PreOmics iST NHS. 

Yes, CHIMERYS 4 is compatible with ion-trap- data generated using HCD or CID fragmentation. While CHIMERYS profits from high-resolution accurate mass (HRAM) spectra, we have seen that CHIMERYS consistently outperforms traditional search engines on ITMS data as well. However, there are some tricks to improve the analysis: we advise using as narrow MS2 fragment tolerances as possible (e.g., 0.25 Da or 0.3 Da instead of 0.5 Da). Second, we recommend using peak filters in the Proteome Discoverer processing workflows for ITMS data. Here, a Top10/Top15/Top20 by 100 Da filter node before the CHIMERYS workflow can help to improve sensitivity and identification rates by removing peaks with low information content from the spectrum before the search. 

CHIMERYS employs a data-driven calibration step during the search. If the initial search does not yield enough high-scoring identifications, CHIMERYS cannot calibrate itself to the data and will stop the calculations. Frequently, this is observed when the chosen settings (e.g. modifications, labels or tolerances) or FASTA file do not match the.RAW file (e.g., wrong MS2 tolerance for the analyzer). Please double-check your settings before opening a support ticket at pd.support@thermofisher.com.

The answer to this question depends on the data analyzed. For MS1-based quantification, CHIMERYS does not perform its own quantitation but utilizes the Minora Feature Detector Node in Proteome Discoverer Software. For MS2 Reporter ion-based quantification (i.e., TMT-based quantification), the Reporter Ion Quantifier Node in Proteome Discoverer is used. For MS2 fragment ion-based quantification as used in DIA or PRM data analysis, CHIMERYS calculates a quantification value by tracing the contribution of a peptide to a series of spectra along the retention time dimension. This value is imported into Proteome Discoverer by the Fragment Ions Quantifier Node. 

Currently, CHIMERYS's data analysis is limited to Thermo Scientific instruments that write the. RAW format. This includes all Thermo Scientific Orbitrap, ion trap, and Orbitrap Astral mass spectrometers.  

We constantly test and monitor the compatibility and performance of the CHIMERYS service. However, in rare cases, CHIMERYS might not perform as expected. If you encounter an issue with CHIMERYS that cannot be attributed to incorrect settings or a broken .RAW file, please open a ticket with pd.support@thermofisher.com. In order to quickly follow up with the search you attempted, please extract the FULL CHIMERYS JOB ID from the Proteome Discoverer Log file (setting Verbose switched on) and communicate this ID to the support staff. 

Your feedback and feature requests concerning CHIMERYS are highly valuable to us. Please feel free to share your thoughts and suggestions with us at info@msaid.de. For feedback and feature requests specific to the Proteome Discoverer software, please get in touch with pd.support@thermofisher.com.

In response to numerous requests for a standalone version of CHIMERYS, we have introduced the MSAID Platform this year. This highly scalable, fully automatable, cloud-based SaaS platform is designed to revolutionize your proteomic data workflow. The MSAID Platform provides scalable storage and processing of proteomics data, powered by the latest CHIMERYS™ 4. It offers convenient web access for data interrogation directly through your browser. Get a free demo and try out the all-new web platform for proteomics.

With CHIMERYS 2.0 in PD 3.1, there's no longer a need to link the Percolator node to the CHIMERYS node. This is because the FDR (False Discovery Rate) estimation is automatically conducted in the cloud. For a faster processing experience, we've replaced the Percolator algorithm with the reimplementation termed. Therefore, there's no requirement for you to include the Percolator node manually. 

To access the MSAID Platform, simply create an account here. With a free account, you'll receive 100 GB of compute and 100 GB of storage, along with access to CHIMERYS 4, our advanced intelligent search algorithm. You'll also get a 30-day trial to explore all the platform's features and capabilities. After the trial period, you can choose from a range of flexible subscription options, including monthly plans or one-time compute and storage packages, to suit your needs.

CHIMERYS on the MSAID Platform can natively process all DDA, DIA and PRM files from Thermo Scientific mass analyzers (e.g. Orbitrap, Astral, Ion Trap). We are currently working on the goal of becoming vendor-independent, by either adding additional software solutions to the platform or by making CHIMERYS accept any open format.

We use Amazon Web Services (AWS) to store and process your proteomics data. Here are several key measures we take to safeguard your information:

- Data locality: The data of our customers is stored in Europe and our service is in accordance with GDPR. We will add other data locations (e.g. US-east, US-west) later, however the data of our European customers will always be stored in the EU.

- Robust Encryption: All data stored on AWS is encrypted at rest and in transit (TLS).

- Compliance and Certifications: AWS complies with major security standards and certifications such as ISO 27001, which helps protect data from security threats or breaches. Certified AWS services include AWS Cognito, AWS S3 storage, AWS EC2 compute that are underlying this platform.

- Access Controls: We implement strict access controls and auditing capabilities. Access to data is tightly controlled and limited to authorized personnel only, based on their role. We also use advanced identity and access management policies to prevent unauthorized access.

- Regular Security Audits: We regularly review and update our security practices. This includes conducting security audits and vulnerability scans to ensure that our defenses remain effective against new threats.

- Data Redundancy: AWS S3 provides high durability via data redundancy. This means your data is automatically replicated across multiple locations to prevent data loss due to hardware failures or other incidents.

By leveraging AWS infrastructure and adhering to best practices, we ensure that your data is secure and protected at all times. If you have any more questions about our data security measures, please feel free to contact us anytime.

No, your proteomic data, no matter if uploaded input data or result data is not shared with anyone. We adhere to a strict policy that prohibits the sharing of your proteomic data with any external companies or third parties. In addition, access to your data is tightly controlled and limited to authorized personnel only. For more information and which data is collected and stored, please review our data privacy notice.