A5035861712- RNA and protein synthesis mechanisms
- Gene Regulatory Network Analysis
- Biofuel production and bioconversion
- Evolution and Genetic Dynamics
- Anaerobic Digestion and Biogas Production
- Microbial Community Ecology and Physiology
- Protein Structure and Dynamics
- Genomics and Phylogenetic Studies
- CRISPR and Genetic Engineering
- Advanced biosensing and bioanalysis techniques
- Bioinformatics and Genomic Networks
- Gene expression and cancer classification
- Evolutionary Algorithms and Applications
- Computational Drug Discovery Methods
- Bacterial Genetics and Biotechnology
- Methane Hydrates and Related Phenomena
- Diffusion and Search Dynamics
- Receptor Mechanisms and Signaling
- Genetics, Bioinformatics, and Biomedical Research
- Origins and Evolution of Life
- Anomaly Detection Techniques and Applications
- Viral Infectious Diseases and Gene Expression in Insects
- RNA Research and Splicing
- 3D Printing in Biomedical Research
- Biomedical and Engineering Education
National Institute of Standards and Technology
2020-2023
National Institute of Standards
2022
University of California, Santa Barbara
2015-2021
Carnegie Mellon University
2005
Molecular evolution can be conceptualized as a walk over "fitness landscape", or the function of fitness (e.g., catalytic activity) space all possible sequences. Understanding requires knowing structure landscape and identifying viable evolutionary pathways through landscape. However, for any biomolecule is largely unknown. The RNA special interest because believed to have been foundational early life. In particular, an essential activity leading genetic code would reaction ribozymes with...
Article30 March 2021Open Access Source DataTransparent process The genotype-phenotype landscape of an allosteric protein Drew S Tack orcid.org/0000-0002-9380-4643 National Institute Standards and Technology, Gaithersburg, MD, USA Search for more papers by this author Peter D Tonner orcid.org/0000-0003-2840-0930 Abe Pressman Nathan Olson orcid.org/0000-0003-2585-3037 Sasha F Levy orcid.org/0000-0002-0923-1636 SLAC Accelerator Laboratory, Menlo Park, CA, Joint Initiative Metrology in Biology,...
Large-scale measurements linking genetic background to biological function have driven a need for models that can incorporate these data reliable predictions and insight into the underlying biophysical system. Recent modeling efforts, however, prioritize predictive accuracy at expense of model interpretability. Here, we present LANTERN (landscape interpretable nonparametric model, https://github.com/usnistgov/lantern ), hierarchical Bayesian distills genotype–phenotype landscape (GPL)...
The metabolism of archaeal methanogens drives methane release into the environment and is critical to understanding global carbon cycling. Methanogenesis operates at a very low reducing potential compared other forms respiration therefore many anaerobic environments. Harnessing or altering methanogen has mitigate warming even be utilized for energy applications.Here, we report draft genome sequences isolated Methanobacterium bryantii, Methanosarcina spelaei, Methanosphaera cuniculi,...
In an earlier paper, outlines of footprints persons walking normally were studied to determine whether different people make verifiably distinct footprints. Our basic null hypothesis is: given a footprint outline trace made by Subject A (Alice), then B (Bob), person, cannot produce indistinguishable from that Alice. We showed in the previous work probability chance match is less than 10(-8). this paper we report two new advances our research. First, establish rigorous mathematical framework...
The emergence of catalytic RNA is believed to have been a key event during the origin life. Understanding how activity distributed across random sequences fundamental estimating probability that would emerge. Here, we analyze in vitro evolution triphosphorylating ribozymes and translate their fitnesses into absolute estimates for hundreds ribozyme families. analysis efficiently identified highly active estimated with good accuracy. evolutionary dynamics follow Fisher's Fundamental Theorem...
Characterizing genotype-phenotype relationships of biomolecules (e.g. ribozymes) requires accurate ways to measure activity for a large set molecules. Kinetic measurement using high-throughput sequencing k-Seq) is an emerging assay applicable in various domains that potentially scales up throughput over 106 unique nucleic acid sequences. However, maximizing the return such assays understanding technical challenges introduced by sequence heterogeneity and DNA sequencing. We characterized...
As synthetic biology expands and accelerates into real-world applications, methods for quantitatively precisely engineering biological function become increasingly relevant. This is particularly true applications that require programmed sensing to dynamically regulate gene expression in response stimuli. However, few have been described can engineer with any level of quantitative precision. Here, we present two complementary precision genetic sensors: silico selection...
Abstract Allostery is a fundamental biophysical mechanism that underlies cellular sensing, signaling, and metabolism. Quantitative methods to characterize the genotype-phenotype relationships for allosteric proteins would provide data needed improve engineering of biological systems, uncover role mis-regulation in disease, develop allosterically targeted drugs 1 . Here we report large-scale measurement landscape an protein: lac repressor from Escherichia coli , LacI. Using method combines...
Abstract Large-scale measurements linking genetic background to biological function have driven a need for models that can incorporate these data reliable predictions and insight into the underlying biochemical system. Recent modeling efforts, however, prioritize predictive accuracy at expense of model interpretability. Here, we present LANTERN ( https://github.com/usnistgov/lantern ), hierarchical Bayesian distills genotype-phenotype landscape (GPL) low-dimensional feature-space represents...
Abstract Allostery is a fundamental biophysical mechanism that underlies cellular sensing, signaling, and metabolism. Yet quantitative understanding of allosteric genotype-phenotype relationships remains elusive. Here we report the large-scale measurement landscape for an protein: lac repressor from Escherichia coli , LacI. Using method combines long-read short-read DNA sequencing, quantitatively measure dose-response curves nearly 10 5 variants LacI genetic sensor. The resulting data...
ABSTRACT Characterization of genotype-phenotype relationships genetically encoded molecules (e.g., ribozymes) requires accurate quantification activity for a large set molecules. Kinetic measurement using high-throughput sequencing k -Seq) is an emerging assay applicable in various domains that potentially scales up throughput to 10 5 ~ 6 unique sequences. However, technical challenges introduced by sequence heterogeneity and DNA must be understood realize the utility limitations such...