What is CluSeek? ClusterSeeker
CluSeek is a versatile tool for identifying gene clusters in GenBank data. It first searches for homologs of two or more user-selected marker genes and identifies regions where these homologs are colocalized within bacterial genomes. The resulting sequences, including the markers and their neighboring genes, are then visualized as gene clusters. These visualized clusters can be further explored and analyzed using CluSeek’s built-in functions through a user-friendly interface.
CluSeek can be applied to any type of gene cluster, regardless of the encoded phenotype, including clusters involved in the biosynthesis of specialized metabolites, secretion systems, complex metabolic pathways, virulence factors, chemotactic motility, and more.
CluSeek enables efficient genome mining of GenBank data using a strategy distinct from mainstream tools such as antiSMASH, which is widely used for specialized metabolite analysis.
Research of specialized Metabolites:
Is CluSeek similar to antiSMASH?
Genome mining of biosynthetic gene clusters is typically performed with tools like antiSMASH. AntiSMASH identifies clusters within individual genomes using predefined rules derived from well-characterized biosynthetic classes. In contrast, CluSeek operates on a fundamentally different principle: it scans the entire GenBank without relying on prior rules, internal libraries, or knowledge of known clusters. In fact, gene clusters identified by CluSeek can subsequently be exported for their analysis with antiSMASH, bridging the two approaches.
Is CluSeek easy to use?
Yes. CluSeek follows a simple download-and-use principle and has a user-friendly graphical interface, making it accessible to users without IT expertise. To help users navigate the interface, we have also prepared step-by-step video tutorials available on YouTube.
HOW TO CITE CLUSEEK:
How can I use CluSeek? Enjoy some practical examples already published:
Practical Examples of CluSeek Usage
- Sowa, S. T., Weddeling, H. G., & Teufel, R. (2026). BisCEET: A Visual Browser for Biosynthetic Gene Clusters Aiding in the Identification of Natural Product Variants and Distinct Tailoring Enzymes. Journal of Natural Products. 89 (5), 1392–1398.
- Sowa, S. T., Weddeling, H. G., & Teufel, R. (2026). Genome Mining-Guided Discovery of the Glycosylated Griseorhodin Congener Ruskamycin. Journal of Natural Products. 89 (5), 1399–1406.
New BisCEET bioinformatic tool builds up on the CluSeek output and it is successfully used for discovery of new compounds. - Bratiichuk, D., Fries, F., Stierhof, M., Morguet, L., Zapp, J., Müsken, M., … & Luzhetskyy, A. (2026). Genome Mining-Driven Isolation of New Gromomycins and Insights into Their Mode of Action. ACS Chemical Biology, 21(3), 546-557.
New variants of Gromomycin biosynthetic gene clusters and their distribution within bacterial taxonomy were identified using CluSeek - Strüder, A., Touzi, S., Long, M., Mingyar, E., Schwitalla, C., Berscheid, A., … & Stegmann, E. (2025). Identification of the negamycin split biosynthetic gene cluster in Kitasatospora purpeofusca ATCC21470. bioRxiv, 2025-07.
The ribosome binding antibiotic negamycin split biosynthetic gene cluster was identified in Kitasatospora purpeofusca - Pfeiffer, I. P. M., Schröder, M. P., Koutsandrea, P. H., Vitale, G. A., Herrera‐Rosero, D., Geibel, C., … & Mordhorst, S. (2025). Peptide Arginases from Cryptic Pathways Install Ornithine Residues in Uncharacterized Members of Orphan RiPP Families. ChemBioChem, 26(24), e202500658.
New RiPP biosynthetic gene clusters employing rare peptide arginases were discovered by bioinformatic search for “DD(I/V)LF”-type precursors found in close proximity to peptide arginases - De Rop, Anne-Sofie, et al. “Digging Deeper : Computational and Functional Screening for Iminosugar Natural Product Enzymes in Soil Bacteria (Meta)Genomes.” Natural Products in the 21st Century, Abstracts, 2026.
New enzymes participating in the biosynthesis of iminosugar containing natural products in soil bacteria (meta)genomes http://hdl.handle.net/1854/LU-01KH8NQ1JJAKFTR20S3DHS71VX (conference poster) - Jan Mašek, Berness Peter Falcao, Lucie Kajan Grodecká, Vojtěch Hudzieczek, Tomáš Galica, Petra Urajová, Roman Sobotka, Lucie Kovářová, Roman Hobza, Pavel Hrouzek (2026). Cyanochelin uptake reveals an exclusively cyanobacterial class of AMIN-domain TonB-dependent transporters bioRxiv 2026.07.30.741596; doi: https://doi.org/10.64898/2026.07.30.741596
- Bruessow, N., Teutsch, D., Mainz, A., Suessmuth, R. D., & Dittmann, E. (2026). An Oligomeric Lanthipeptide from Nostoc punctiforme Promotes Host Association During Early Symbiosis with Blasia pusilla. bioRxiv, 2026-08. doi: https://doi.org/10.64898/2026.08.14.744816
Are there any limitations to using CluSeek?
CluSeek was developed for prokaryotic genomes; however, preliminary testing shows that it can also handle sequencing data from eukaryotes. It is fully compatible with Windows and macOS, and is also accessible on Linux via a Python package.
Troubleshooting issues with failed NCBI downloads
We have recently become aware of an issue with NCBI servers, which can cause larger queries to fail (XML parsing errors or incomplete reads), even ones that previously worked without issue. We are looking into how to best fix this. In the meantime, our two suggestions are:
- Try running your marker protein searches one by one from the BLASTP web UI ( blast.ncbi.nlm.nih.gov/Blast.cgi ), download the XML output and then input them into CluSeek. Note that you must set the target database to nr and increase the number of returned proteins from 100 to 5000 if you desire any meaningful search depth.
- Try running your search during low server load times, eg. during the weekend.
If you’re willing to risk a shallower search, you can also consider:
- Limiting your search to a narrower range of taxonomic groups via an ENTREZ query (accessible via BLASTP options).
- Reducing the maximum number of results from the default 5000.
The issue appears to be caused by data downloads from NCBI that are over a certain size failing. Our best guess is that this is caused either by a file size cap or a download timing out.
Please also let us know via e-mail if either workaround did (or did not) work for you – we’re always happy to help you get your analysis through while we work on mitigating this as much as possible. Either way, hopefully within a few weeks we will have a fixed version available.
Can I set up CluSeek now?
Yes! The latest version is 2.0.2 – check below
Windows
The windows setup is the most straightforward.
- Download CluSeek for Windows here.
- Extract the zip file.
- If you are setting up CluSeek for the first time, install the Windows redistributables (vc_redist.x86) packaged with CluSeek – or get the latest version from microsoft. If they are already installed, there is no problem.
- That’s it, you can just run CluSeek.exe by double clicking it.
Note that you may get a security warning due to running an unsigned executable. This is a false alarm; you can ignore this message and continue. We are aware of this and are currently looking into it.
MacOS
While CluSeek can run on MacOS, currently it gets blocked for security reasons when simply downloaded from the internet. Depending on your MacOS version, you may be able to create an exception for it – but especially if you are using a newer Mac, you may also not be. We are currently working on getting a signing key from Apple to solve this issue. For now, you can try this workaround:
- Download CluSeek for MacOS on a Windows machine.
- Extract the zip file.
- Use a USB drive to copy CluSeek from your Windows machine to your Mac.
- Run CluSeek.
This workaround appears to work because at least some MacOS only block files downloaded directly from the internet – but place no such restrictions on other methods such as USB drives.
Also note that CluSeek relies on osx-64 emulation to work on newer Macs. The operating system should run it inside an emulator by default, but it is possible you may need to force it.
Please let us know via e-mail if this workaround helped – we’re always happy to help our users with any technical issues.
Linux
While we do not explicitly package CluSeek for any Linux distribution, we do maintain a Python package on PyPi. See the section below for details.
Python package
A python package named cluseek is available via PyPi. The package works out of the box on Windows and Linux, but requires workarounds on newer MacOS (see below). It can be used to run the GUI application as with the previous methods. CluSeek currently has no CLI and was not intended for use in python scripts as a module (although that feature is coming, eventually).
- Create a new Python environment (via venv or similar) and activate it.
pip install cluseekpython -m cluseek
This will start the GUI application.
You can find our source code on GitHub.
Note for Windows
As with the portable executable, make sure you have installed the Windows x86 redistributables , otherwise sequence alignment .
Workaround for MacOS
The cause of the issue on Mac is simple. CluSeek still uses Qt5/PySide2 for its GUI, which only supports old x86_64 Intel processors, not the new Apple silicon (M1, M2, … etc.). Of course, new Macs have an emulator to solve this issue, but things get tricky when python packages enter the picture. It seems that pip will only try to install pacakges compatible with the new processors, and will refuse to grab the old osx-64 ones. Probably the simplest way around this is to use conda instead
conda create –platform osx-64 –name cluseek_env python=3.9conda activate cluseek_envpip install cluseekpython -m cluseek
We are not currently working on porting CluSeek to Qt6/PySide6 to solve this issue, however if you’d find it useful, let us know via e-mail.
Video tutorials are available on our YouTube channel.
CluSeek v2.0.2
Minor changes:
– Hidden the abort button in the download dialog until abort functionality can be re-worked
– Hidden unused radio button “Other” in the protein group network view
Bug fixes:
– Updated FASTA protein export user-specified identifiers for clusters, not the internal numerical ones
– Fixed offline mode button
– Included coding sequence strand information in the GenBank format export
Cosmetic changes:
– Adjusted UI alignment in the colocalization histogram
– Changed spelling of E-value in colocalization histogram
– Changed capitalization for drop down menus on the toolbar
– Corrected typo in the Cluster view screen
– Rewrote some error messages to improve clarity
You can send us your feedback or suggestions at (old e-mail address is not functioning anymore!)