Please read all three senior officials’ resignation letters in full. I couldn’t even find quotes to pull. All three are cornerstones of modern public health. Dan Jernigan’s been at CDC longer than I’ve been alive. Department leadership left them in an impossible position.

There are other hits in our dataset, so I hope this may help others working on the same questions. I also hope our method is broadly useful to others!

We further characterize the importance of transcription to an interferon response, consistent with prior work from Richard Randall, and newer work from AJ te Velthuis and Jonathan Yewdell.
pubmed.ncbi.nlm.nih.gov/24478437/
www.science.org/doi/10.1126/...
pubmed.ncbi.nlm.nih.gov/39605425/

Applying our system to infection with flu virus lacking an innate immune antagonist, we identify the NELF complex as significantly enhancing interferon transcription. Digging in mechanistically we find that inactivating this complex increases flu transcription, increasing viral RNA.

By taking the ratio of the signal RNA to the integration events (sequencing the DNA) we can infer if an edit increases, decreases, or does nothing to our test promoter.

By hooking up our promoter of interest upstream of a promoter driving a CRISPR guide, when our promoter is active a longer "signal" RNA is generated.

There are prior genome-wide screens, but they are pretty labor intensive and involve cell sorting. Taking a note from a method developed in yeast called CiBER-Seq developed by Nicholas Ingolia's group, and CROP-seq, developed by Christopher Bock's group, we developed a sequencing-only approach.

So what did we do? We are deeply interested into the inputs of the cellular event of viral detection and the production of interferons. Our prior work largely focused on viral variation, but we wanted to look into host processes that influence this event.

I also want to thank all three anonymous reviewers. If you saw the first preprint I hope you will agree it was much improved by their careful critiques. The review process was everything one could want.

As a still somewhat junior PI (less every day) I feel so incredibly lucky to have had the support and patience of my more senior colleagues.

I also want to thank our editor, Anice Lowen, and editorial board member Harmit Malik. Anice was also the editor on Alison's other paper in PLoS Pathogens. Her willingness to shepherd our papers through the review process is deeply appreciated.

Before giving a synopsis I want to give credit to the hard work of all of the authors (which I am fortunate enough to have them all from my group), particularly our lab alum, and my first graduate student, Alison Vicary.