Jumper enables discontinuous transcript assembly in coronaviruses

Abstract

Genes in SARS-CoV-2 and other viruses in the order of Nidovirales are expressed by a process of discontinuous transcription which is distinct from alternative splicing in eukaryotes and is mediated by the viral RNA-dependent RNA polymerase. Here, we introduce the DISCONTINUOUS TRANSCRIPT ASSEMBLYproblem of finding transcripts and their abundances given an alignment of paired-end short reads under a maximum likelihood model that accounts for varying transcript lengths. We show, using simulations, that our method, JUMPER, outperforms existing methods for classical transcript assembly. On short-read data of SARS-CoV-1, SARS-CoV-2 and MERS-CoV samples, we find that JUMPER not only identifies canonical transcripts that are part of the reference transcriptome, but also predicts expression of non-canonical transcripts that are supported by subsequent orthogonal analyses. Moreover, application of JUMPER on samples with and without treatment reveals viral drug response at the transcript level. As such, JUMPER enables detailed analyses of Nidovirales transcriptomes under varying conditions.

A safety framework for flow decomposition problems via integer linear programming

“…In fact, one could even add additional constraints to to further restrict the solution space. For example, some ILP models from Dias et al (2022b) and Sashittal et al (2021) handle the case when the input also contains a set of paths ( subpath constraints ) that must appear in at least one of the k solution paths; we will explain these constraints later.…”

“…This is an NP-hard problem, even when restricted to DAGs ( Vatinlen et al 2008 , Hartman et al 2012 ). Various approaches have been proposed to tackle the problem, including fixed-parameter tractable algorithms ( Kloster et al 2018 ), approximation algorithms ( Mumey et al 2015 , Cáceres et al 2022b ), and integer linear programming (ILP) formulations ( Sashittal et al 2021 , Dias et al 2022b ). In Bioinformatics applications, reads, or contigs originating from a mixed sample of genomic sequences, with different abundances, are aligned to a reference.…”

Efficient Minimum Flow Decomposition via Integer Linear Programming

“…Although the conference version of this article was in print, the recent RNA transcript assembly method JUMPER (Sashittal et al, 2021 ) was brought to our attention. JUMPER appears to be, to our knowledge, the only prior method incorporating the search for paths in a DAG into an ILP.…”