Dataset Information

Using antibodies to control DNA-templated chemical reactions.

ABSTRACT: DNA-templated synthesis takes advantage of the programmability of DNA-DNA interactions to accelerate chemical reactions under diluted conditions upon sequence-specific hybridization. While this strategy has proven advantageous for a variety of applications, including sensing and drug discovery, it has been so far limited to the use of nucleic acids as templating elements. Here, we report the rational design of DNA templated synthesis controlled by specific IgG antibodies. Our approach is based on the co-localization of reactants induced by the bivalent binding of a specific IgG antibody to two antigen-conjugated DNA templating strands that triggers a chemical reaction that would be otherwise too slow under diluted conditions. This strategy is versatile, orthogonal and adaptable to different IgG antibodies and can be employed to achieve the targeted synthesis of clinically-relevant molecules in the presence of specific IgG biomarker antibodies.

SUBMITTER: Baranda Pellejero L

PROVIDER: S-EPMC7721721 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Using antibodies to control DNA-templated chemical reactions.

Baranda Pellejero Lorena L Mahdifar Malihe M Ercolani Gianfranco G Watson Jonathan J Brown Tom T Ricci Francesco F

Nature communications 20201207 1

DNA-templated synthesis takes advantage of the programmability of DNA-DNA interactions to accelerate chemical reactions under diluted conditions upon sequence-specific hybridization. While this strategy has proven advantageous for a variety of applications, including sensing and drug discovery, it has been so far limited to the use of nucleic acids as templating elements. Here, we report the rational design of DNA templated synthesis controlled by specific IgG antibodies. Our approach is based o ...[more]

PMID: 33288745

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Project description:BackgroundEnzymatic and chemical reactions are key for understanding biological processes in cells. Curated databases of chemical reactions exist but these databases struggle to keep up with the exponential growth of the biomedical literature. Conventional text mining pipelines provide tools to automatically extract entities and relationships from the scientific literature, and partially replace expert curation, but such machine learning frameworks often require a large amount of labeled training data and thus lack scalability for both larger document corpora and new relationship types.ResultsWe developed an application of Snorkel, a weakly supervised learning framework, for extracting chemical reaction relationships from biomedical literature abstracts. For this work, we defined a chemical reaction relationship as the transformation of chemical A to chemical B. We built and evaluated our system on small annotated sets of chemical reaction relationships from two corpora: curated bacteria-related abstracts from the MetaCyc database (MetaCyc_Corpus) and a more general set of abstracts annotated with MeSH (Medical Subject Headings) term Bacteria (Bacteria_Corpus; a superset of MetaCyc_Corpus). For the MetaCyc_Corpus, we obtained 84% precision and 41% recall (55% F1 score). Extending to the more general Bacteria_Corpus decreased precision to 62% with only a four-point drop in recall to 37% (46% F1 score). Overall, the Bacteria_Corpus contained two orders of magnitude more candidate chemical reaction relationships (nine million candidates vs 68,0000 candidates) and had a larger class imbalance (2.5% positives vs 5% positives) as compared to the MetaCyc_Corpus. In total, we extracted 6871 chemical reaction relationships from nine million candidates in the Bacteria_Corpus.ConclusionsWith this work, we built a database of chemical reaction relationships from almost 900,000 scientific abstracts without a large training set of labeled annotations. Further, we showed the generalizability of our initial application built on MetaCyc documents enriched with chemical reactions to a general set of articles related to bacteria.

Dataset Information

Using antibodies to control DNA-templated chemical reactions.

Publications

Using antibodies to control DNA-templated chemical reactions.

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