ArticleNature communications2020
UMI-linked consensus sequencing enables phylogenetic analysis of directed evolution.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed.
- Combinatorial Optimization of Protein Systems in Synthetic Cells.ACS synthetic biology · 2026Article
- Oxford Nanopore enhanced accuracy of long-read amplicons applied to microbial whole-genome sequencing.Microbiology spectrum · 2026Article
- Umi-pipeline-nf: a modular and scalable workflow for UMI-tagged nanopore amplicon analysis with real-time sequencing integration and GPU-acceleration.Bioinformatics (Oxford, England) · 2026Article
- UMI-nea: a fast, robust tool for reference-free UMI deduplication and accurate quantification.Bioinformatics (Oxford, England) · 2025Article
- Rapid discovery of monoclonal antibodies by microfluidics-enabled FACS of single pathogen-specific antibody-secreting cells.Nature biotechnology · 2025Article
- Fluorogenic, Subsingle-Turnover Monitoring of Enzymatic Reactions Involving NAD(P)H Provides a Generalized Platform for Directed Ultrahigh-Throughput Evolution of Biocatalysts in Microdroplets.Journal of the American Chemical Society · 2025Article
- Navigating triplet repeats sequencing: concepts, methodological challenges and perspective for Huntington's disease.Nucleic acids research · 2025Review
- Continuous evolution of user-defined genes at 1 million times the genomic mutation rate.Science (New York, N.Y.) · 2024Article
- Nanopore sequencing with unique molecular identifiers enables accurate mutation analysis and haplotyping in the complex lipoprotein(a) KIV-2 VNTR.Genome medicine · 2024Article
- Ultrahigh Throughput Evolution of Tryptophan Synthase in Droplets via an Aptamer Sensor.ACS catalysis · 2024Article
- Enhancing prime editor activity by directed protein evolution in yeast.Nature communications · 2024Article
- Continuous directed evolution of a compact CjCas9 variant with broad PAM compatibility.Nature chemical biology · 2024Article
- Quantification of evolved DNA-editing enzymes at scale with DEQSeq.Genome biology · 2023Article
- Ultrahigh-Throughput Enzyme Engineering and Discovery inChemical reviews · 2023Review
- Ultra-High-Throughput Absorbance-Activated Droplet Sorting for Enzyme Screening at Kilohertz Frequencies.Analytical chemistry · 2023Article
- Deep mutational scanning: A versatile tool in systematically mapping genotypes to phenotypes.Frontiers in genetics · 2023Review
- High-Throughput Steady-State Enzyme Kinetics Measured in a Parallel Droplet Generation and Absorbance Detection Platform.Analytical chemistry · 2022Article
- Inducible directed evolution of complex phenotypes in bacteria.Nucleic acids research · 2022Article
- In vivo hypermutation and continuous evolution.Nature reviews. Methods primers · 2022Article
- Ultrahigh-Throughput Detection of Enzymatic Alcohol Dehydrogenase Activity in Microfluidic Droplets with a Direct Fluorogenic Assay.Chembiochem : a European journal of chemical biology · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The success of protein evolution campaigns is strongly dependent on the sequence context in which mutations are introduced, stemming from pervasive non-additive interactions between a protein's amino acids ('intra-gene epistasis'). Our limited understanding of such epistasis hinders the correct prediction of the functional contributions and adaptive potential of mutations. Here we present a straightforward unique molecular identifier (UMI)-linked consensus sequencing workflow (UMIC-seq) that simplifies mapping of evolutionary trajectories based on full-length sequences. Attaching UMIs to gene variants allows accurate consensus generation for closely related genes with nanopore sequencing. We exemplify the utility of this approach by reconstructing the artificial phylogeny emerging in three rounds of directed evolution of an amine dehydrogenase biocatalyst via ultrahigh throughput droplet screening. Uniquely, we are able to identify lineages and their founding variant, as well as non-additive interactions between mutations within a full gene showing sign epistasis. Access to deep and accurate long reads will facilitate prediction of key beneficial mutations and adaptive potential based on in silico analysis of large sequence datasets.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.