CUBAP: an interactive web portal for analyzing codon usage biases across populations

Abstract

Synonymous codon usage significantly impacts translational and transcriptional efficiency, gene expression, the secondary structure of both mRNA and proteins, and has been implicated in various diseases. However, population-specific differences in codon usage biases remain largely unexplored. Here, we present a web server, https://cubap.byu.edu, to facilitate analyses of codon usage biases across populations (CUBAP). Using the 1000 Genomes Project, we calculated and visually depict population-specific differences in codon frequencies, codon aversion, identical codon pairing, co-tRNA codon pairing, ramp sequences, and nucleotide composition in 17,634 genes. We found that codon pairing significantly differs between populations in 35.8% of genes, allowing us to successfully predict the place of origin for African and East Asian individuals with 98.8% and 100% accuracy, respectively. We also used CUBAP to identify a significant bias toward decreased CTG pairing in the immunity related GTPase M (IRGM) gene in East Asian and African populations, which may contribute to the decreased association of rs10065172 with Crohn's disease in those populations. CUBAP facilitates in-depth gene-specific and codon-specific visualization that will aid in analyzing candidate genes identified in genome-wide association studies, identifying functional implications of synonymous variants, predicting population-specific impacts of synonymous variants and categorizing genetic biases unique to certain populations.

Leucine encoding codon TTG shows an inverse relationship with GC content in genes involved in neurodegeneration with iron accumulation

“…Rare synonymous variants in 4 genes (CDH23, SLC9A3R1, RHBDD2, and ITIH2) were studied in 67 Caribbean Hispanic families affected with Alzheimer's disease, found at a higher frequency in comparison to reference population of the same ancestry and contribute to Alzheimer etiology [42]. The codon usage might differ in population and elucidate how susceptible a population is to an ailment [43].…”

ExtRamp Online: Enabling ramp sequence calculations via an intuitive web interface.

“…We previously developed ExtRamp , which is the only algorithm to identify gene-speci c translational ramp sequences in silico. Notably, ExtRamp has been used to identify ramp sequence conservation across all domains of life (McKinnon, et al, 2021; and population-speci c ramp sequences within different human populations (Hodgman, et al, 2020). However, ExtRamp currently is limited to command-line applications, which require users to navigate various options that are tailored toward genome-wide analyses.…”

CompoDynamics: a comprehensive database for characterizing sequence composition dynamics

“…Over the past two decades, several valuable resources have been developed to characterize biomolecular sequence composition ( 16–21 ). Among them, representative resources are CUTG ( 16 ), CBCB ( 17 ), HIVE-CUTs ( 18 ) and CUBAP ( 21 ). Specifically, CUTG ( 16 ), established in 1998, is a widely used database compiling codon usage for 3 027 973 CDSs for 35 799 genomes (including 8,233 chloroplast genomes, 12 271 mitochondrion genomes and 439 plastid genomes).…”

“…HIVE-CUTs ( 18 ) contains 855 412 codon usage tables for 689 420 species and their mitochondrial/plastid genomes derived from GenBank and RefSeq. The webserver CUBAP ( 21 ) computes GC content and codon usage for 17 634 human genes and facilitates analyses of CUB across human populations. In addition, there are still several other resources that specialize in integration of protein physicochemical properties ( 22 , 23 ) and phase separation properties ( 24–26 ).…”