I'll admit that I haven't read all the research papers on DELs, so this question may be answered in that literature. How does the assay account for possible interactions between the DNA tag and the target protein? It would seem there is a high chance for non-specific interactions to occur between the protein target and DNA label which would confound the compound binding data. A secondary assay which tests compounds in the absence of DNA tags would be confirmatory, but I assume that hasn't been done for the ~500,000 binders per protein in this set simply due to time and cost constraints.
", "messages": [ { "id": "2772035", "postDate": "04/24/2024 14:01:04", "content": "I'll admit that I haven't read all the research papers on DELs, so this question may be answered in that literature. How does the assay account for possible interactions between the DNA tag and the target protein? It would seem there is a high chance for non-specific interactions to occur between the protein target and DNA label which would confound the compound binding data. A secondary assay which tests compounds in the absence of DNA tags would be confirmatory, but I assume that hasn't been done for the ~500,000 binders per protein in this set simply due to time and cost constraints.
", "rawMarkdown": "I'll admit that I haven't read all the research papers on DELs, so this question may be answered in that literature. How does the assay account for possible interactions between the DNA tag and the target protein? It would seem there is a high chance for non-specific interactions to occur between the protein target and DNA label which would confound the compound binding data. A secondary assay which tests compounds in the absence of DNA tags would be confirmatory, but I assume that hasn't been done for the ~500,000 binders per protein in this set simply due to time and cost constraints.", "votes": null }, { "id": "2773786", "postDate": "04/24/2024 22:27:55", "content": "https://www.kaggle.com/competitions/leash-BELKA/discussion/493500#2750855
\nNot sure the exact controls, but there were controls run
", "rawMarkdown": "https://www.kaggle.com/competitions/leash-BELKA/discussion/493500#2750855\n\nNot sure the exact controls, but there were controls run", "votes": null }, { "id": "2773973", "postDate": "04/25/2024 02:16:40", "content": "Thanks for the link. In that post they describe repeatability, but I'm wondering if the DNA primer/barcode could potentially interact with the protein itself. Since each compound has a unique set of building blocks as well as unique DNA sequences corresponding to those building blocks, it might be impossible to determine whether binding originated from the small molecule or the barcode. I've not seen how they control for that possibility, however.
", "rawMarkdown": "Thanks for the link. In that post they describe repeatability, but I'm wondering if the DNA primer/barcode could potentially interact with the protein itself. Since each compound has a unique set of building blocks as well as unique DNA sequences corresponding to those building blocks, it might be impossible to determine whether binding originated from the small molecule or the barcode. I've not seen how they control for that possibility, however.", "votes": null }, { "id": "2775470", "postDate": "04/25/2024 17:06:59", "content": "We use multiple DNA tags for each building block so that we can control for this. We have seen proteins where the DNA sequence makes a big difference, but we did not see that effect for these three proteins.
", "rawMarkdown": "We use multiple DNA tags for each building block so that we can control for this. We have seen proteins where the DNA sequence makes a big difference, but we did not see that effect for these three proteins.", "votes": null }, { "id": "2775913", "postDate": "04/25/2024 21:54:05", "content": "Thanks for that detail.
\nI suppose if you were targeting a DNA binding protein (e.g., transcription factor, histone) it would be fraught with false positives. Interesting technology.
", "rawMarkdown": "Thanks for that detail.\n\nI suppose if you were targeting a DNA binding protein (e.g., transcription factor, histone) it would be fraught with false positives. Interesting technology.", "votes": null } ], "comments": [ { "id": 2773786, "author_name": "chemdatafarmer", "author_url": "", "post_date": "04/24/2024 22:27:55", "content": "https://www.kaggle.com/competitions/leash-BELKA/discussion/493500#2750855
\nNot sure the exact controls, but there were controls run
", "votes": null, "replies": [ { "id": 2773973, "author_name": "kirkdco", "author_url": "", "post_date": "04/25/2024 02:16:40", "content": "Thanks for the link. In that post they describe repeatability, but I'm wondering if the DNA primer/barcode could potentially interact with the protein itself. Since each compound has a unique set of building blocks as well as unique DNA sequences corresponding to those building blocks, it might be impossible to determine whether binding originated from the small molecule or the barcode. I've not seen how they control for that possibility, however.
", "votes": null, "replies": [ { "id": 2775470, "author_name": "andrewdblevins", "author_url": "", "post_date": "04/25/2024 17:06:59", "content": "We use multiple DNA tags for each building block so that we can control for this. We have seen proteins where the DNA sequence makes a big difference, but we did not see that effect for these three proteins.
", "votes": null, "replies": [ { "id": 2775913, "author_name": "kirkdco", "author_url": "", "post_date": "04/25/2024 21:54:05", "content": "Thanks for that detail.
\nI suppose if you were targeting a DNA binding protein (e.g., transcription factor, histone) it would be fraught with false positives. Interesting technology.
", "votes": null, "replies": [] } ] } ] } ] } ], "raw_markdown_by_id": { "2772035": "I'll admit that I haven't read all the research papers on DELs, so this question may be answered in that literature. How does the assay account for possible interactions between the DNA tag and the target protein? It would seem there is a high chance for non-specific interactions to occur between the protein target and DNA label which would confound the compound binding data. A secondary assay which tests compounds in the absence of DNA tags would be confirmatory, but I assume that hasn't been done for the ~500,000 binders per protein in this set simply due to time and cost constraints.", "2773786": "https://www.kaggle.com/competitions/leash-BELKA/discussion/493500#2750855\n\nNot sure the exact controls, but there were controls run", "2773973": "Thanks for the link. In that post they describe repeatability, but I'm wondering if the DNA primer/barcode could potentially interact with the protein itself. Since each compound has a unique set of building blocks as well as unique DNA sequences corresponding to those building blocks, it might be impossible to determine whether binding originated from the small molecule or the barcode. I've not seen how they control for that possibility, however.", "2775470": "We use multiple DNA tags for each building block so that we can control for this. We have seen proteins where the DNA sequence makes a big difference, but we did not see that effect for these three proteins.", "2775913": "Thanks for that detail.\n\nI suppose if you were targeting a DNA binding protein (e.g., transcription factor, histone) it would be fraught with false positives. Interesting technology." }, "source": "meta" }