Publications by authors named "Nicholas K Lee"

Article Synopsis
  • The binding of transcription factors to gene regions like promoters and enhancers is key for regulating genes, but figuring out how these elements work is tough.
  • A new tool called scover uses convolutional neural networks trained on single-cell data to identify regulatory motifs and assess their importance for gene expression.
  • Scover reveals that it accounts for 29% of gene expression variation in mouse tissues and can identify specific regulatory activities in distal enhancers of the developing human brain, making the results more understandable.
View Article and Find Full Text PDF

Deep neural networks (DNNs) hold promise for functional genomics prediction, but their generalization capability may be limited by the amount of available data. To address this, we propose EvoAug, a suite of evolution-inspired augmentations that enhance the training of genomic DNNs by increasing genetic variation. Random transformation of DNA sequences can potentially alter their function in unknown ways, so we employ a fine-tuning procedure using the original non-transformed data to preserve functional integrity.

View Article and Find Full Text PDF

Microfluidic platforms use controlled fluid flows to provide physiologically relevant biochemical and biophysical cues to cultured cells in a well-defined and reproducible manner. Undisturbed flows are critical in these systems, and air bubbles entering microfluidic channels can lead to device delamination or cell damage. To prevent bubble entry into microfluidic channels, we report a low-cost, Rapidly Integrated Debubbler (RID) module that is simple to fabricate, inexpensive, and easily combined with existing experimental systems.

View Article and Find Full Text PDF

Identifying potential protein-ligand interactions is central to the field of drug discovery as it facilitates the identification of potential novel drug leads, contributes to advancement from hits to leads, predicts potential off-target explanations for side effects of approved drugs or candidates, as well as de-orphans phenotypic hits. For the rapid identification of protein-ligand interactions, we here present a novel chemogenomics algorithm for the prediction of protein-ligand interactions using a new machine learning approach and novel class of descriptor. The algorithm applies Bayesian Additive Regression Trees (BART) on a newly proposed proteochemical space, termed the bow-pharmacological space.

View Article and Find Full Text PDF

Cyanobacteria produce structurally and functionally diverse polyketides, nonribosomal peptides and their hybrids. Sfp-type phosphopantetheinyl transferases (PPTases) are essential to the production of these compounds via functionalizing carrier proteins (CPs) of biosynthetic megaenzymes. However, cyanobacterial Sfp-type PPTases remain poorly characterized, posing a significant barrier to the exploitation of cyanobacteria for biotechnological and biomedical applications.

View Article and Find Full Text PDF

The transition from prelife where self-replication does not occur, to life which exhibits self-replication and evolution, has been a subject of interest for many decades. Membranes, forming compartments, seem to be a critical component of this transition as they provide several concurrent benefits. They maintain localized interactions, generate electro-chemical gradients, and help in selecting cooperative functions as they arise.

View Article and Find Full Text PDF