Life in the middle
As a bioinformatics applications scientist, I work in a middle ground between those who develop code for analyzing next-gen sequencing data and those who consume that analysis. The developers are often people trained in computer science, mathematics, and statistics. The consumers are often people trained in biology and medicine. There is some overlap, of course, but if you’ll allow a broad generalization, I think the two groups (developers and consumers) are separated by large cultural differences in science.
Ensemble focus vs. single-gene focus
I think one of the biggest differences from my experience is the approach to conceptualizing the results of a next-gen seq experiment (e.g., RNA-seq). People on the methods side tend to think in terms of ensembles and distributions. They are interested in how the variation observed across all 30,000 genes can be modeled and used to estimate differential expression. They are interested in concepts like shrinkage estimators, bayesian priors, and hypothesis weighting. The table of differentially expressed features is thought to have meaning mainly in the statistical analysis of pathway enrichment (another ensemble).
Conversely, biologists have a drastically different view. Often they care about a single gene or a handful of genes and how those genes vary across conditions of interest in the system that they are studying. This is a rational response to the complexity of biological systems; no one can keep the workings of hundreds of genes in mind. In order to make progress, you must focus. However, this narrow focus leads investigators to sometimes cherry pick results pertaining to their ‘pet’ genes. This can invest those results with more meaning than is warranted from a single experiment.
The gene-focus of biologists also leads to clashes with the ensemble-focus of bioinformatics software. For example, major DE analysis packages like DESeq2 do not have convenience functions to make volcano plots, even though I’ve found that those kinds of plots are the most useful and easiest to understand for biologists. Sleuth does have a volcano plotting function, but doesn’t allow for labeling genes. In my experience, however, biologists want a high-res figure with common name gene labels (not ensemble transcript IDs) that they can circle and consider for wet lab validation.
New software to address the divide?
I am hopeful about the recent release of the new “bcbioRNASeq” package from Harvard Chan school bioinformatics (developers of ‘bcbio’ RNA-seq pipeline software). It appears to be a step towards making it easier for people like me to walk on both sides of this cultural divide. The package takes all of the outputs of the ‘bcbio’ pipeline and transforms them into an accessible S4 object that can be operated on quickly and simply within R.
Most importantly, the ‘bcbioRNASeq’ module allows for improved graphics and plotting that make communication with biologists easier. For example, the new MA and volcano plots appear to be based on ‘ggplot2’ graphics and are quite pretty (and have text label options(!), not shown here):
I still need to become familiar with the ‘bcbioRNASeq’ package, but it looks quite promising. ‘pcaExplorer‘ is another R/Bioconductor package that I feel does a great job of making accessible RNA-seq reports quickly and easy. I suspect we will see continued improvements to make plots prettier and more informative, with an increasing emphasis on interactive, online plots and notebooks rather than static images.