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Hudson, C. M.

Publications and source records attributed to Hudson, C. M..

3 recordsLinked to original sources

GROQ-seq Datasets Across Transcription Factors (LacI, RamR, VanR), T7 RNA Polymerase and TEV Protease

Predicting any proteins function from its sequence alone would be a significant breakthrough in molecular biology. Although machine learning approaches have sought to tackle this, their limited generalizability reflects the absence of sufficiently large, open, diverse, and unified datasets. To address this data gap, we developed a high-throughput experimental platform called GROQ-seq (Growth-based Quantitative Sequencing). In GROQ-seq, a proteins function can be linked to a sequencing-based readout that enables scalable characterization of large variant libraries in Escherichia coli. Here, we present pilot datasets demonstrating its performance across three distinct protein function classes: transcription factors, polymerases, and proteases. The objective of this report is to present the datasets and to provide users with a clear and transparent characterization of their properties, including both the strengths and limitations.

bioengineering↗

New candidates for regulated gene integrity revealed through precise mapping of integrative genetic elements

Integrative genetic elements (IGEs) are mobile multigene DNA units that integrate into and excise from host bacterial chromosomes. Each IGE usually targets a specific site within a conserved host gene, integrating in a manner that preserves target gene function. However, a small number of bacterial genes are known to be inactivated upon IGE integration and reactivated upon excision, regulating phenotypes of virulence, mutation rate, and terminal differentiation in multicellular bacteria. The list of regulated gene integrity (RGI) cases has been slow-growing because IGEs have been challenging to precisely and comprehensively locate in genomes. We present software (TIGER) that maps IGEs with unprecedented precision and without attB site bias. TIGER uses a comparative genomic, ping-pong BLAST approach, based on the principle that the IGE integration module (i.e., its int-attP region) is cohesive. The resultant IGEs, along with integrase phylogenetic analysis and gene inactivation tests, revealed 19 new cases of genes whose integrity is regulated by IGEs (including dut, eccCa1, gntT, hrpB, merA, ompN, prkA, tqsA, traG, yifB, yfaT and ynfE), as well as recovering previously known cases (in sigK, spsM, comK, mlrA, and hlb genes). It also recovered known clades of site-promiscuous integrases and identified possible new ones.

bioinformatics↗

RetSynth: Solving all optimal retrosynthesis solutions using dynamically constrained integer linear programming

MotivationNaive determination of all the optimal pathways to production of a target chemical on an arbitrarily defined chassis organism is computationally intractable. Methods like linear integer programming can provide a singular solution to this problem, but fail to provide all optimal pathways.\n\nResultsHere we present RetSynth, an algorithm for determining all optimal biological retrosynthesis solutions, given a starting biological chassis and target chemical. By dynamically scaling constraints, additional pathway search scales relative to the number of fully independent branches in the optimal pathways, and not relative to the number of reactions in the database or size of the metabolic network. This feature allows all optimal pathways to be determined for a very large number of chemicals and for a large corpus of potential chassis organisms.\n\nAvailabilityThis algorithm is distributed as part of the RetSynth software package, under a BSD 2-clause license at https://www.github.com/sandialabs/RetSynth/

synthetic biology↗