Trajectory-based differential expression analysis for single-cell sequencing data

Trajectory inference has radically enhanced single-cell RNA-seq research by enabling the study of dynamic changes in gene expression. Downstream of trajectory inference, it is vital to discover genes that are (i) associated with the lineages in the trajectory, or (ii) differentially expressed between lineages, to illuminate the underlying biological processes. Current data analysis procedures, however, either fail to exploit the continuous resolution provided by trajectory inference, or fail to pinpoint the exact types of differential expression. We introduce tradeSeq, a powerful generalized additive model framework based on the negative binomial distribution that allows flexible inference of both within-lineage and between-lineage differential expression. By incorporating observation-level weights, the model additionally allows to account for zero inflation. We evaluate the method on simulated datasets and on real datasets from droplet-based and full-length protocols, and show that it yields biological insights through a clear interpretation of the data. Downstream of trajectory inference for cell lineages based on scRNA-seq data, differential expression analysis yields insight into biological processes. Here, Van den Berge et al. develop tradeSeq, a framework for the inference of within and between-lineage differential expression, based on negative binomial generalized additive models

Clustering as an example of optimizing arbitrarily chosen objective functions

This paper is a reflection upon a common practice of solving various types of learning problems by optimizing arbitrarily chosen criteria in the hope that they are well correlated with the criterion actually used for assessment of the results. This issue has been investigated using clustering as an example, hence a unified view of clustering as an optimization problem is first proposed, stemming from the belief that typical design choices in clustering, like the number of clusters or similarity measure can be, and often are suboptimal, also from the point of view of clustering quality measures later used for algorithm comparison and ranking. In order to illustrate our point we propose a generalized clustering framework and provide a proof-of-concept using standard benchmark datasets and two popular clustering methods for comparison