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sgRNACNN: identifying sgRNA on-target activity in four crops using ensembles of convolutional neural networks.

Plant molecular biology
We proposed an ensemble convolutional neural network model to identify sgRNA high on-target activity in four crops and we used one-hot encoding and k-mers for sequence encoding. As an important component of the CRISPR/Cas9 system, single-guide RNA (s...

Systematic characterization of mutations altering protein degradation in human cancers.

Molecular cell
The ubiquitin-proteasome system (UPS) is the primary route for selective protein degradation in human cells. The UPS is an attractive target for novel cancer therapies, but the precise UPS genes and substrates important for cancer growth are incomple...

A machine learning-based framework for modeling transcription elongation.

Proceedings of the National Academy of Sciences of the United States of America
RNA polymerase II (Pol II) generally pauses at certain positions along gene bodies, thereby interrupting the transcription elongation process, which is often coupled with various important biological functions, such as precursor mRNA splicing and gen...

HSM6AP: a high-precision predictor for the Homo N6-methyladenosine (m^6 A) based on multiple weights and feature stitching.

RNA biology
Recent studies have shown that RNA methylation modification can affect RNA transcription, metabolism, splicing and stability. In addition, RNA methylation modification has been associated with cancer, obesity and other diseases. Based on information ...

Identification of SARS-CoV-2 viral entry inhibitors using machine learning and cell-based pseudotyped particle assay.

Bioorganic & medicinal chemistry
In response to the pandemic caused by SARS-CoV-2, we constructed a hybrid support vector machine (SVM) classification model using a set of publicly posted SARS-CoV-2 pseudotyped particle (PP) entry assay repurposing screen data to identify novel pote...

Screening of a novel free fatty acid receptor 1 (FFAR1) agonist peptide by phage display and machine learning based-amino acid substitution.

Biochemical and biophysical research communications
Free fatty acid receptor 1 (FFAR1 or GPR40) has attracted attention for the treatment of type 2 diabetes mellitus, and various small-molecule agonists have been developed. However, most FFAR1 agonists as well as endogenous ligands, such as linoleic a...

An Integrated Approach toward NanoBRET Tracers for Analysis of GPCR Ligand Engagement.

Molecules (Basel, Switzerland)
Gaining insight into the pharmacology of ligand engagement with G-protein coupled receptors (GPCRs) under biologically relevant conditions is vital to both drug discovery and basic research. NanoLuc-based bioluminescence resonance energy transfer (Na...

Enhancing CRISPR-Cas9 gRNA efficiency prediction by data integration and deep learning.

Nature communications
The design of CRISPR gRNAs requires accurate on-target efficiency predictions, which demand high-quality gRNA activity data and efficient modeling. To advance, we here report on the generation of on-target gRNA activity data for 10,592 SpCas9 gRNAs. ...

A deep learning approach to identify gene targets of a therapeutic for human splicing disorders.

Nature communications
Pre-mRNA splicing is a key controller of human gene expression. Disturbances in splicing due to mutation lead to dysregulated protein expression and contribute to a substantial fraction of human disease. Several classes of splicing modulator compound...

Deep and accurate detection of m6A RNA modifications using miCLIP2 and m6Aboost machine learning.

Nucleic acids research
N6-methyladenosine (m6A) is the most abundant internal RNA modification in eukaryotic mRNAs and influences many aspects of RNA processing. miCLIP (m6A individual-nucleotide resolution UV crosslinking and immunoprecipitation) is an antibody-based appr...