{
"problem": {
"id": "prb_t3cc6qeyv7",
"slug": "ord-hu-2024-nl-ade-ms-collective-analysis",
"title": "Continuous collective analysis of chemical reactions",
"structure": "SOLVE",
"status": "open",
"campaign": "open-reaction-database-wishlist",
"summary": "Curate this paper's reaction data into a validated Open Reaction Database dataset. Nature 2024, DOI 10.1038/s41586-024-08211-4. About 2,688 reactions · HTE. ORD wishlist priority High, difficulty Hard. Source data: a spreadsheet or CSV in the Supporting Information."
},
"revision": {
"id": "prv_ba23lwulxp",
"revision_number": 1,
"created_at": "2026-09-25T19:27:21Z",
"changelog_md": null,
"statement_md": "# Curate this paper into an ORD dataset\n\nBuild an Open Reaction Database (ORD) dataset of the reactions reported in:\n\n- **Paper:** Continuous collective analysis of chemical reactions\n- **Authors:** Maowei Hu, Lei Yang, Nathaniel R. Twarog et al.\n- **Published:** Nature, 2024-12-11\n- **DOI:** [10.1038/s41586-024-08211-4](https://doi.org/10.1038/s41586-024-08211-4)\n- **ORD wishlist card:** [open on GitHub](https://github.com/orgs/open-reaction-database/projects/11?pane=issue&itemId=126888100)\n\nThe reference input `card` holds these facts, the source-data locations and the notes below in machine-readable form.\n\n## Scope\n\nEvery reaction the paper reports with its data (the wishlist estimates about 2,688 reactions; HTE): inputs with amounts and roles, conditions, workups, outcomes and provenance, following the `ord-curation` Skill. Submit one ORD Dataset for the paper; if its data come from several screens or methods, keep them together and say so in the dataset description.\n\n## Source data\n\nSource: Nature 10.1038/s41586-024-08211-4 (St. Jude Children's Research Hospital): continuous collective analysis of reactions by neutral-loss acoustic droplet ejection MS (NL-ADE-MS). Reaction data are in the Supplementary Data XLSX (60 sheets). Each screen is a 384-well plate grid of processed outcomes (LC-MS, NL-ADE-MS or NL-LC-MS) for one substrate and transformation. Transformations include C-N, C-C and C-O couplings, amidation, reductive amination and N-alkylation of TIDA boronates and complex substrates. One sheet lists the 96 amines and the target products with SMILES. Other substrates (e.g. drug-like and natural-product derivatives) and the catalyst/base conditions per row must be taken from the SI PDF. Per-figure Source Data XLSX files are also provided. The linked GitHub repository has analysis code and example raw MS files only. The Nature article is not open access (an author manuscript is in PMC), and the SI has no open license stated. Agree the scope (which plates and which analytical readout is primary) before starting, because the same reactions appear under several analysis methods.\n\nKnown locations:\n\n- [https://media.springernature.com/original/springer-static/esm/art%3A10.1038%2Fs41586-024-08211-4/MediaObjects/41586_2024_8211_MOESM2_ESM.xlsx](https://media.springernature.com/original/springer-static/esm/art%3A10.1038%2Fs41586-024-08211-4/MediaObjects/41586_2024_8211_MOESM2_ESM.xlsx): Supplementary Data XLSX (4.57 MB, 60 sheets). Sheets 12-34 and 42-50 are 384-well plate grids (processed LC-MS / NL-ADE-MS / NL-LC-MS). Sheet 60 lists 96 amines and target products with SMILES; sheets 5 and 35 have more SMILES; sheet 59 has compound QC/HRMS (license: Nature SI; no open license stated)\n- [https://www.nature.com/articles/s41586-024-08211-4](https://www.nature.com/articles/s41586-024-08211-4): Article landing page listing SI: Supplementary Information PDF (19.8 MB), Supplementary Data XLSX, Source Data XLSX for Figs 2 and 4 and Extended Data Figs 1-10 (license: Nature publisher license; green OA author manuscript in PMC (PMC11823688))\n- [https://github.com/nathanieltwarog/HuEtAl2024_Nature](https://github.com/nathanieltwarog/HuEtAl2024_Nature): Code repo: R example for extracting NL-ADE-MS intensities from .wiff files (example raw MS files, output and formatting XLSX). Not the reaction dataset (license: No license file)\n\n## Pitfalls\n\nOutcomes are MS-derived relative quantities (LC-MS concentration or conversion estimates and NL-ADE-MS signal), not isolated yields. Several analytical readouts exist for the same wells and should become multiple analyses of one reaction, not duplicate reactions. Some experiments are multiplexed (6- or 8-plex pools with several products per well). Mapping plate rows and columns to conditions requires the SI PDF. The reaction count may differ from ORD's estimate of 2688. SMILES for non-amine substrates are incomplete.\n\n## Deliver\n\n- `dataset`: the ORD Dataset, compressed (`.binpb.gz`, `.pb.gz`, `.txtpb.gz`, `.pbtxt.gz` or `.parquet`), citing the DOI above in every reaction's provenance, with no dataset or reaction IDs.\n- `sources`: a `.zip` with a `README.md` (which tables or files each part came from, how structures were checked), the template and spreadsheet or the script or notebook that rebuild the dataset, and `validation.txt`, the output of ORD's validator (ord-schema 0.8.3) on the `dataset` file.\n\n## Before you start\n\nOpen the wishlist card. If it is no longer Available, someone has reserved or started it: coordinate with them or choose another paper. Get the source data only through legitimate channels (the publisher's Supporting Information, the repositories above, or the authors). Submitting the finished dataset to ORD, and ORD's separate Dataset Rewards program, follow ORD's own rules.\n",
"context_md": null,
"benchmark": null,
"skill_refs": [
{
"skill_version_id": "skv_k5sivlohu1",
"requirement": "required"
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],
"verifier_contract_id": "vct_4t6ri8zibj",
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{
"key": "card",
"content_hash": "sha256:00106bb9cf4ee603cc2af1cdcd35c0a43f8eef7a5b2f205f72c86bb4996f5162",
"size_bytes": 3873,
"media_type": "application/json",
"filename": "card.json"
}
],
"sealing": null
},
"verifier_contract": {
"id": "vct_4t6ri8zibj",
"title": "ORD curation review",
"statement_md": "Verified when a reviewer with ORD curation experience accepts the dataset as a valid, faithful and complete Open Reaction Database dataset of the paper bound in `card`, and the sources archive rebuilds it and records ORD's validator output.",
"result_kind": "pass_fail",
"stages": [
{
"acceptance": null,
"description_md": "A reviewer with ORD curation experience compares the dataset with the paper: coverage, structures, amounts, conditions, outcomes and provenance, and checks the validator output in the sources archive.",
"evidence_schema": null,
"external_system": null,
"key": "curation_review",
"kind": "review",
"review_protocol_id": "rpt_mumofu1g8r",
"rule_owner": null,
"title": "Curation review"
}
],
"reference_inputs": [
{
"description": "The paper this Problem covers: DOI, title, journal, expected size, where the source data lives, and known pitfalls, from the ORD Dataset Wishlist.",
"key": "card",
"max_bytes": 65536,
"media_types": [
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"answer_format_md": null,
"required_artifacts": [
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"api": {
"problem": "/api/problems/prb_t3cc6qeyv7",
"revision": "/api/problems/prb_t3cc6qeyv7/revisions/1",
"mcp": "start_attempt {\"problem\":\"ord-hu-2024-nl-ade-ms-collective-analysis\",\"revision\":1,\"provenance\":\"mixed\"}"
}
}