The main goal of the Common Mechanism is to provide a free, open-source, easy-to-use tool that will give every DNA provider access to affordable synthesis screening, helping to universalize screening practices globally.

Affordable commercial DNA synthesis is an essential service that supports the growing bioeconomy and is critically important for a wide range of biotechnology advances. However, synthetic DNA can be used to construct pandemic pathogens and other dangerous biological agents. Many providers of synthetic DNA screen the orders they receive to ensure that access to dangerous DNA is only given to those with a legitimate scientific use for it and adequate risk management procedures and practices in place. DNA providers that belong to the International Gene Synthesis Consortium publicly commit to voluntarily screen synthesis orders and customers, but these companies only represent an estimated 80% of global synthesis market share. That means approximately one in five orders likely go unscreened. At present, screening is not legally required by any national government–though some governments are beginning to explore stronger incentives for screening As the cost of DNA synthesis continues to decline over time, the fixed costs of screening orders is placing a growing financial burden on commercial providers and straining the viability of the voluntary screening model.

The Common Mechanism is part of an emerging ecosystem of screening tools, and IBBIS shares a goal with many other providers of increasing the fraction of global orders that are screened, as well as universalizing established best practices for screening. IBBIS' contribution, the Common Mechanism, is meant to be an open, global baseline for DNA synthesis screening. The baseline synthesis screening capabilities provided by the Common Mechanism are available for free, and the sequence screening software is designed to be installed locally by individual providers, lowering barriers to access while protecting customer data.

Built with sequence databases that incorporate regulated sequences from many different countries, the Common Mechanism provides a more comprehensive global screening approach. Our biorisk screening approach, which integrates many examples to build a sequence profile for each publicly available biorisk sequence, has been validated for resistance to AI-based evasion attempts, enhancing security against sophisticated threats. As a custom-built tool, the Common Mechanism receives regular updates to reflect evolving definitions of biorisk sequences, ensuring users always have access to current screening methodologies.

The Common Mechanism was designed with input from an international Technical Consortium, and its ongoing development will continue to involve international experts. IBBIS actively participates in international efforts to develop standards for defining sequences of concern, meaning the Common Mechanism consistently reflects the most up-to-date consensus on screening approaches. The Common Mechanism sequence screening software is open source, and the customer screening tools were released under Creative Commons Licenses. IBBIS welcomes ideas for improving any of our screening tools.

The Common Mechanism was initially proposed in 2020 by an international working group jointly convened by the Nuclear Threat Initiative (NTI) and the World Economic Forum (WEF), which also called for an international entity that will house the mechanism, promote its adoption, and work to establish global norms for nucleic acid synthesis screening. Later that year, NTI and WEF launched the Technical Consortium to inform the design of the Common Mechanism, consisting of African, Asian, European and North American experts from industry, academia, philanthropy, and international organizations. From 2020–2023, this Consortium guided the design of the baseline Common Mechanism screening process, and its ongoing development will continue to involve international experts. The Common Mechanism software and databases were developed by a team of technical consultants working with NTI, led by Dr. Nicole Wheeler of the University of Birmingham, and including contributions from Brittany Rife Magalis of the University of Louisville, Jennifer Lu of the Center for Computational Biology at Johns Hopkins University and our own Technical Lead, Tessa Alexanian. In 2024, IBBIS was launched to act as a long-term home for the Technical Consortium and Common Mechanism, as well as to support related initiatives in advancing biosecurity.

The Common Mechanism has its long-term home within IBBIS, a Switzerland-based independent international organization that has received funding from philanthropic organizations based in Europe and North America.

The Common Mechanism screens sequences that are 50 nucleotides or longer and flags both “sequences of concern” (i.e. virulence factors and toxins) and sequences that may be subject to export controls. The software produces three different screening outputs: flagged sequences of concern, areas of similarity to regulated pathogens, and matches to genes with a known benign function. Sequences of concern are identified by comparing order sequences against a 'biorisk' database equipped with machine learning models capturing profiles of sequences of concern, specifically those publicly known to be associated with toxicity or pathogenicity and limited to sequences found in regulated, listed pathogens and toxins. Similarity to regulated pathogens is identified by comparing the order against publicly available DNA and protein sequences to retrieve the organism with the most closely matching genome, then cross-referencing matches with international control lists. Benign and housekeeping genes are identified using a curated ‘benign’ database that draws from sequences found in thousands of bacterial species, RNA sequences that participate in processes essential for life, and sequences submitted to the iGEM parts registry with no associated safety flags. This process is shown in the flowchart below.

While all screening outputs are reported, the Common Mechanism will provide an overall “pass” or “flag” decision for an order according to the flowchart below.

The Common Mechanism will allow all nucleic acid synthesis companies to adopt baseline screening practices at no cost beyond computing, and to maintain screening in-house, without the need to send their customers’ sequences outside of the company.

No, anyone can use the software. It can be useful for researchers, DNA synthesis customers, and end users. We encourage you to use it if you are unsure whether your provider or third-party vendor conducts screening or if you want to better understand any risks associated with your sequence.

The Common Mechanism is designed to screen DNA and RNA sequences. While it can handle standard sequences, there are some limitations:

• It cannot currently screen protein sequences directly, though translations of the input DNA sequences are screened as part of the process.

• The system does not have specialized functionality for screening oligo orders.

• Each input sequence in the FASTA file is screened individually.

• The pipeline cannot currently process sequences containing ambiguity codons.

• It cannot screen sequences shorter than 50 nucleotides

IBBIS is constantly working on reducing these restrictions, which should gradually disappear as new updates are released.

When running the software in fast mode, a single run typically takes only a few seconds. However, when performing a full search using NCBI databases, it may take several minutes to generate the final output files, depending on your machine's computational power.

The Common Mechanism currently supports sequences stored in both FASTA (.fasta) and plain text (.txt) formats.

The current version of the software does not support multiple sequence screening, but we are working on implementing this feature soon.

Yes, the Common Mechanism is designed with integration capabilities in mind. It includes a "fast mode" that is specifically designed to enable our sensitive biorisk detection to be incorporated into other pipelines that may use different approaches for flagging sequences of concern through taxonomic measures. Since the Common Mechanism is available as a Python package and can be run on Linux systems, it can be readily incorporated into standard bioinformatics pipelines. The software’s modular design allows for flexible implementation, where users can utilize specific components of the Common Mechanism that best complement their existing workflows.

The Common Mechanism sequence screening was developed with a dual emphasis on reducing ambiguities and flagging a baseline level of sequences of concern, making it a useful tool for benchtop synthesis devices. The decision support tool is able to provide a fully automated “flag” or “pass” decision for each order; benchtop devices could then be configured to refuse to synthesize sequences that are flagged during screening. Legitimate users of those sequences would need to order them from another commercial provider or provide an authentication key that allows them to synthesize specific sequences of concern.

Yes, the software is open-source, and you can inspect the code and databases online.

Installing the Common Mechanism sequence screening software requires a computing environment which can run shell scripts and Python with adequate storage space for the databases used (~1 Gb for the curated biorisk and benign databases, ~600 Gb for the standard protein and nucleotide databases used for similarity search, which will already be installed in many bioinformatics computing environments). It is also possible to install and run the program with Biocontainer (Docker image). Since the release of this document, the software has only been extensively tested in Linux computing environments, although trials in Windows and MacOS demonstrated its capacity to run in these operating systems as well. We expect to make available an API for testing small numbers of sequences in the near future.

No. The Common Mechanism is designed to be locally installed by synthesis providers, keeping all customer information in-house and ensuring that your data is protected. The output files generated by the software are stored locally and are not sent to IBBIS or any third party.

The initial “biorisk” database used by the Common Mechanism draws only from existing, publicly available databases of sequences known to be associated with toxicity or pathogenicity. This list is further limited to only those sequences that are found in regulated, listed pathogens and toxins, such as those on export control lists. This limited biorisk database allows the Common Mechanism to flag sequences that are well established, transparently sourced, and represent some level of international consensus. As such, sharing the initial databases does not present a security concern.

No, IBBIS does not request or collect any personal information from users during installation. The only metrics we have access to is the number of downloads the software has via Bioconda.

The Common Mechanism was designed to adhere to the most comprehensive DNA screening guidelines currently available: the Framework for Nucleic Acid Synthesis Screening of the United States, the UK screening guidance on synthetic nucleic acids for users and providers, the Harmonized Screening Protocol of the International Gene Synthesis Consortium and ISO 20688-2:2024.

Database updates are released when there are major updates to our source databases, in response to vulnerability disclosures, and when definitions of biological risk change. Historically, we have released database updates at least once per year. We are planning to transition to a quarterly maintenance update schedule to provide more frequent improvements and ensure the screening remains aligned with rapidly evolving biosecurity requirements. Users will be notified of available updates through our GitHub repository and communications channels.

For general inquiries, please get in touch with IBBIS at info@ibbis.bio. Our technical staff and consultants are available to support users of the sequence screening software and will guide you through the installation process if needed; feel free to contact us if you are interested in using it.

If you are a provider, do not proceed with the synthesis and contact the customer to request clarification on their motive for ordering that particular sequence. When doing so, we recommend using our SOC Order Form, which follows our customer legitimacy verification guidelines. If you are a customer, end user, or principal user, be transparent about your intentions and clearly indicate the status of your sequence when placing an order with your provider.

If you experience a bug during installation or when using the software, you can open an issue on GitHub and our team will address it as soon as possible.

Although unlikely, if a known benign sequence is flagged or if a sequence with a previously identified risk is not, please contact us at screening@ibbis.bio and explain the situation.

While the Common Mechanism provides robust DNA synthesis screening capabilities, the software currently has a few limitations users should be aware of:

• Processing speed: When running comprehensive searches using NCBI databases, the software may require significant processing time depending on your computational resources.

• Database size requirements: The software depends on large reference databases (~600 GB for standard protein and nucleotide databases), which may present storage challenges for some users.

• Oligonucleotide handling: The system does not currently have specialized functionality for screening oligo orders.

• Scope: The Common Mechanism is focused solely on sequence screening and does not provide customer screening capabilities. For guidance on customer screening, please refer to our customer legitimacy verification guidelines.

IBBIS is constantly working on reducing these limitations, which should gradually disappear as new updates are released.

When citing the Common Mechanism in academic publications or presentations, please use the following reference:

Wheeler et al., "Overcoming Challenges to Developing a Common Global Baseline for Nucleic Acid Synthesis Screening," Applied Biosafety, 2024.

For software-specific citations, please refer to our GitHub repository.

Yes, software users may display our logo or wordmark in presentations, talks, documents, or papers when explaining how they used it. We prefer that the commec wordmark is used when specifically talking about your usage of the software.