A5041338859- RNA and protein synthesis mechanisms
- Genomics and Phylogenetic Studies
- RNA modifications and cancer
- Protein Structure and Dynamics
- RNA Research and Splicing
- Genetics, Bioinformatics, and Biomedical Research
- Bacteriophages and microbial interactions
- Bacterial Genetics and Biotechnology
- Biochemical and Structural Characterization
- Evolution and Genetic Dynamics
- Seed and Plant Biochemistry
- Glycosylation and Glycoproteins Research
- Pluripotent Stem Cells Research
- Plant Molecular Biology Research
- Enzyme Structure and Function
- Machine Learning in Bioinformatics
- Photosynthetic Processes and Mechanisms
- 3D Printing in Biomedical Research
- Lipid metabolism and biosynthesis
- Neuroscience and Neural Engineering
- Monoclonal and Polyclonal Antibodies Research
Center for Systems Biology
2016-2024
Harvard University
2015-2024
Instituto Superior Politécnico Metropolitano de Angola
2019
Donald Danforth Plant Science Center
2013
Abstract The ability to design functional sequences and predict effects of variation is central protein engineering biotherapeutics. State-of-art computational methods rely on models that leverage evolutionary information but are inadequate for important applications where multiple sequence alignments not robust. Such include the prediction variant indels, disordered proteins, proteins such as antibodies due highly variable complementarity determining regions. We introduce a deep generative...
Coevolutionary sequence analysis has become a commonly used technique for de novo prediction of the structure and function proteins, RNA, protein complexes. We present EVcouplings framework, fully integrated open-source application Python package coevolutionary analysis. The framework enables generation alignments, calculation evaluation evolutionary couplings (ECs), mutation effects. combination an easy to use, flexible command line interface underlying modular makes full power analyses...
Abstract A major challenge in protein design is to augment existing functional proteins with multiple property enhancements. Altering several properties likely necessitates numerous primary sequence changes, and novel methods are needed accurately predict combinations of mutations that maintain or enhance function. Models co-variation (e.g., EVcouplings), which leverage extensive information about various activities from homologous sequences, have proven effective for many applications...
Summary Heterotrimeric G ‐proteins consisting of α, β and γ subunits play an integral role in mediating multiple signalling pathways plants. A novel, recently identified plant‐specific protein, AGG 3, has been proposed to be important regulator organ size mediator stress responses rabidopsis, whereas its potential homologs rice are major quantitative trait loci for seed panicle branching. To evaluate the 3 towards oil yield improvement, gene was overexpressed C amelina sativa , oilseed crop...
The ability to rewrite large stretches of genomic DNA enables the creation new organisms with customized functions. However, few methods currently exist for accumulating such widespread changes in a single organism. In this study, we demonstrate rapid approach rewriting bacterial genomes modified synthetic DNA. We recode 200 kb Salmonella typhimurium LT2 genome through process term SIRCAS (stepwise integration rolling circle amplified segments), towards constructing an attenuated and...
Abstract The ability to design functional sequences and predict effects of variation is central protein engineering biotherapeutics. State-of-art computational methods rely on models that leverage evolutionary information but are inadequate for important applications where multiple sequence alignments not robust. Such include the prediction variant indels, disordered proteins, proteins such as antibodies due highly variable complementarity determining regions. We introduce a deep generative...
Abstract Designing optimized proteins is important for a range of practical applications. Protein design rapidly developing field that would benefit from approaches enable many changes in the amino acid primary sequence, rather than small number mutations, while maintaining structure and enhancing function. Homologous protein sequences contain extensive information about various properties activities have emerged over billions years evolution. Evolutionary models sequence co-variation,...
Abstract The functions of proteins and RNAs are determined by a myriad interactions between their constituent residues, but most quantitative models how molecular phenotype depends on genotype must approximate this simple additive effects. While recent have relaxed constraint to also account for pairwise interactions, these approaches do not provide tractable path towards modeling higher-order dependencies. Here, we show latent variable with nonlinear dependencies can be applied capture...
Abstract Summary Coevolutionary sequence analysis has become a commonly used technique for de novo prediction of the structure and function proteins, RNA, protein complexes. This approach requires extensive computational pipelines that integrate multiple tools, databases, data processing steps. We present EVcouplings framework, fully integrated open-source application Python package coevolutionary analysis. The framework enables generation alignments, calculation evaluation evolutionary...
The functions of proteins and RNAs are determined by a myriad interactions between their constituent residues, but most quantitative models how molecular phenotype depends on genotype must approximate this simple additive effects. While recent have relaxed constraint to also account for pairwise interactions, these approaches do not provide tractable path towards modeling higher-order dependencies. Here, we show latent variable with nonlinear dependencies can be applied capture...
Non-coding RNAs are ubiquitous, but the discovery of new RNA gene sequences far outpaces research on their structure and functional interactions. We mine evolutionary sequence record to derive precise information about function RNA-protein complexes. As in protein prediction, we use maximum entropy global probability models co-variation infer evolutionarily constrained nucleotide-nucleotide interactions within molecules, nucleotide-amino acid The predicted contacts allow all-atom blinded 3D...
Genome recoding will provide a deeper understanding of genetics and transform biotechnology. We bypass the reliance previous genome methods on site-specific enzymes demonstrate rapid recombineering based strategy for writing genomes by Stepwise Integration Rolling Circle Amplified Segments (SIRCAS). installed largest number codon substitutions in single organism yet published, creating strain Salmonella typhimurium with 1557 leucine changes across 200 kb genome.