The Ramp Atlas: facilitating tissue and cell-specific ramp sequence analyses through an intuitive web interface.

Ramp sequences occur when the average translational efficiency of codons near the 5' end of highly expressed genes is significantly lower than the rest of the gene sequence, which counterintuitively increases translational efficiency by decreasing downstream ribosomal collisions. Here, we show that the relative codon adaptiveness within different tissues changes the existence of a ramp sequence without altering the underlying genetic code. We present the first comprehensive analysis of tissue and cell type-specific ramp sequences and report 3108 genes with ramp sequences that change between tissues and cell types, which corresponds with increased gene expression within those tissues and cells. The Ramp Atlas (https://ramps.byu.edu/) allows researchers to query precomputed ramp sequences in 18 388 genes across 62 tissues and 66 cell types and calculate tissue-specific ramp sequences from user-uploaded FASTA files through an intuitive web interface. We used The Ramp Atlas to identify seven SARS-CoV-2 genes and seven human SARS-CoV-2 entry factor genes with tissue-specific ramp sequences that may help explain viral proliferation within those tissues. We anticipate that The Ramp Atlas will facilitate personalized and creative tissue-specific ramp sequence analyses for both human and viral genes that will increase our ability to utilize this often-overlooked regulatory region.

MCMICRO: a scalable, modular image-processing pipeline for multiplexed tissue imaging.

Highly multiplexed tissue imaging makes detailed molecular analysis of single cells possible in a preserved spatial context. However, reproducible analysis of large multichannel images poses a substantial computational challenge. Here, we describe a modular and open-source computational pipeline, MCMICRO, for performing the sequential steps needed to transform whole-slide images into single-cell data. We demonstrate the use of MCMICRO on tissue and tumor images acquired using multiple imaging platforms, thereby providing a solid foundation for the continued development of tissue imaging software.

Pairwise Correlation Analysis of the Alzheimer's Disease Neuroimaging Initiative (ADNI) Dataset Reveals Significant Feature Correlation.

The Alzheimer's Disease Neuroimaging Initiative (ADNI) contains extensive patient measurements (e.g., magnetic resonance imaging [MRI], biometrics, RNA expression, etc.) from Alzheimer's disease (AD) cases and controls that have recently been used by machine learning algorithms to evaluate AD onset and progression. While using a variety of biomarkers is essential to AD research, highly correlated input features can significantly decrease machine learning model generalizability and performance. Additionally, redundant features unnecessarily increase computational time and resources necessary to train predictive models. Therefore, we used 49,288 biomarkers and 793,600 extracted MRI features to assess feature correlation within the ADNI dataset to determine the extent to which this issue might impact large scale analyses using these data. We found that 93.457% of biomarkers, 92.549% of the gene expression values, and 100% of MRI features were strongly correlated with at least one other feature in ADNI based on our Bonferroni corrected α (p-value ≤ 1.40754 × 10-13). We provide a comprehensive mapping of all ADNI biomarkers to highly correlated features within the dataset. Additionally, we show that significant correlation within the ADNI dataset should be resolved before performing bulk data analyses, and we provide recommendations to address these issues. We anticipate that these recommendations and resources will help guide researchers utilizing the ADNI dataset to increase model performance and reduce the cost and complexity of their analyses.

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

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.