Proximity Ligation Resource

For more information, please check out the pre-print:

Synthetic community Hi-C benchmarking provides a baseline for virus-host inferences

https://www.biorxiv.org/content/10.1101/2025.02.12.637985v2

Recommendations

As Hi-C proximity ligation becomes more widely adopted, it is important to assess whether a Z-score threshold of ≥ 0.5 is broadly generalizable. While our SynCom data show that this threshold effectively filters spurious linkages, these results are based on controlled marine virus-host systems. The underlying principle of Hi-C, cross-linking physically proximal DNA fragments, should theoretically allow its application across diverse environments. However, natural systems may introduce variability that impacts the reliability of this threshold.

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To support the responsible use of Hi-C for virus-host linkage inference, we offer the following recommendations:

1. Benchmarking and Cross-validation: Hi-C predictions should be cross-validated with in silico tools, and any discrepancies carefully examined.
   
   
2. Z-score Filtering: Z-score thresholds should, where possible, be guided by SynCom-based benchmarking. In new environments or with poorly characterized taxa, this means conducting controlled benchmarking experiments. Where such benchmarking is not feasible, limitations should be transparently acknowledged, and associated databases annotated to avoid propagating uncertain results.
   
   
3. Threshold Selection: The trade-off between specificity and sensitivity should be calibrated to the research question. Stricter thresholds are warranted for bold claims (e.g., cross-phyla or cross-domain linkages), while broader ecological assessments may allow more lenient filtering.
   
   

To facilitate consistency in future work, we provide a centralized database for researchers (here) to self-report basic methodological details, promoting transparency and reproducibility across studies. We will be updating this resource with new literature every 6-12 months as funding allows.

Please contact sullivan.948 at osu in order for us to add your details here!

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