RNA-Seq technology allows for high-throughput, low cost measurement of gene expression. An important step in this process is the assembly of mRNA transcript short reads into full transcripts. The problem can be viewed as a flow decomposition problem in which the objective is to minimize the number of path flows needed to represent a given flow. In this work we relax the edge flow constraints to allow for some uncertainty in their measurement. We formulate this as the Inexact Flow Decomposition problem and propose an algorithmic strategy to solve it. In practice, real biological data has measurement errors and so experimentally-derived edge-weighted splice graphs are often not flows. The proposed method is the first approach to this problem that explicitly controls the error allowed on each edge in these graphs in order to achieve a flow. In an intermediate step, the method solves an exact flow decomposition instance; if a greedy method is used for this step, the overall running time is $O(\vert E\vert^{2}\vert V\vert^{2}+\vert P\vert^{3})$ , where $P$ is the solution found to the flow decomposition instance. Preliminary results on simulated biological data sets show that in many cases the ground truth paths can be recovered at approximately correct abundances, even with noisy input data.

Flow network decomposition is a natural model for problems where we are given a flow network arising from superimposing a set of weighted paths and would like to recover the underlying data, i.e., decompose the flow into the original paths and their weights. Thus, variations on flow decomposition are often used as subroutines in multiassembly problems such as RNA transcript assembly. In practice, we frequently have access to information beyond flow values in the form of subpaths, and many tools incorporate these heuristically. But despite acknowledging their utility in practice, previous work has not formally addressed the effect of subpath constraints on the accuracy of flow network decomposition approaches. We formalize the flow decomposition with subpath constraints problem, give the first algorithms for it, and study its usefulness for recovering ground truth decompositions. For finding a minimum decomposition, we propose both a heuristic and an FPT algorithm. Experiments on RNA transcript datasets show that for instances with larger solution path sets, the addition of subpath constraints finds 13% more ground truth solutions when minimal decompositions are found exactly, and 30% more ground truth solutions when minimal decompositions are found heuristically.

Recent work provides the first method to measure the relative fitness of genomic variants within a population that scales to large numbers of genomes. A key component of the computation involves finding maximal perfect haplotype blocks from a set of genomic samples for which SNPs (single-nucleotide polymorphisms) have been called. Often, owing to low read coverage and imperfect assemblies, some of the SNP calls can be missing from some of the samples. In this work, we consider the problem of finding maximal perfect haplotype blocks where some missing values may be present. Missing values are treated as wildcards, and the definition of maximal perfect haplotype blocks is extended in a natural way. We provide an output-linear time algorithm to identify all such blocks and demonstrate the algorithm on a large population SNP dataset. Our software is publicly available.

Minimum flow decomposition (MFD) is the NP-hard problem of finding a smallest decomposition of a network flow/circulation X on a directed graph G into weighted source-to-sink paths whose weighted sum equals X . We show that, for acyclic graphs, considering the width of the graph (the minimum number of paths needed to cover all of its edges) yields advances in our understanding of its approximability. For the version of the problem that uses only non-negative weights, we identify and characterise a new class of width-stable graphs, for which a popular heuristic is a O (log Val ( X ))-approximation ( Val ( X ) being the total flow of X ), and strengthen its worst-case approximation ratio from \(\Omega (\sqrt {m})\) to Ω ( m /log m ) for sparse graphs, where m is the number of edges in the graph. We also study a new problem on graphs with cycles, Minimum Cost Circulation Decomposition (MCCD), and show that it generalises MFD through a simple reduction. For the version allowing also negative weights, we give a (⌈ log ‖ X ‖ ⌉ +1)-approximation (‖ X ‖ being the maximum absolute value of X on any edge) using a power-of-two approach, combined with parity fixing arguments and a decomposition of unitary circulations (‖ X ‖ ≤ 1), using a generalised notion of width for this problem. Finally, we disprove a conjecture about the linear independence of minimum (non-negative) flow decompositions posed by Kloster et al. [ 2018 ], but show that its useful implication (polynomial-time assignments of weights to a given set of paths to decompose a flow) holds for the negative version.