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Anna Kuosmanen

Publications and source records attributed to Anna Kuosmanen.

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Using Minimum Path Cover to Boost Dynamic Programming on DAGs: Co-Linear Chaining Extended

Aligning sequencing reads on graph representations of genomes is an important ingredient of pan-genomics. Such approaches typically find a set of local anchors that indicate plausible matches between substrings of a read to subpaths of the graph. These anchor matches are then combined to form a (semi-local) alignment of the complete read on a subpath. Co-linear chaining is an algorithmically rigorous approach to combine the anchors. It is a well-known approach for the case of two sequences as inputs. Here we extend the approach so that one of the inputs can be a directed acyclic graph (DAGs), e.g. a splicing graph in transcriptomics or a variant graph in pan-genomics. This extension to DAGs turns out to have a tight connection to the minimum path cover problem, asking for a minimum-cardinality set of paths that cover all the nodes of a DAG. We study the case when the size $k$ of a minimum path cover is small, which is often the case in practice. First, we propose an algorithm for finding a minimum path cover of a DAG $(V,E)$ in $O(k|E|\log|V|)$ time, improving all known time-bounds when $k$ is small and the DAG is not too dense. Second, we introduce a general technique for extending dynamic programming (DP) algorithms from sequences to DAGs. This is enabled by our minimum path cover algorithm, and works by mimicking the DP algorithm for sequences on each path of the minimum path cover. This technique generally produces algorithms that are slower than their counterparts on sequences only by a factor $k$. Our technique can be applied, for example, to the classical longest increasing subsequence and longest common subsequence problems, extended to labeled DAGs. Finally, we apply this technique to the co-linear chaining problem. We also implemented the new co-linear chaining approach. Experiments on splicing graphs show that the new method is efficient also in practice.

cs.DS

A Novel Combinatorial Method for Estimating Transcript Expression with RNA-Seq: Bounding the Number of Paths

RNA-Seq technology offers new high-throughput ways for transcript identification and quantification based on short reads, and has recently attracted great interest. The problem is usually modeled by a weighted splicing graph whose nodes stand for exons and whose edges stand for split alignments to the exons. The task consists of finding a number of paths, together with their expression levels, which optimally explain the coverages of the graph under various fitness functions, such least sum of squares. In (Tomescu et al. RECOMB-seq 2013) we showed that under general fitness functions, if we allow a polynomially bounded number of paths in an optimal solution, this problem can be solved in polynomial time by a reduction to a min-cost flow program. In this paper we further refine this problem by asking for a bounded number k of paths that optimally explain the splicing graph. This problem becomes NP-hard in the strong sense, but we give a fast combinatorial algorithm based on dynamic programming for it. In order to obtain a practical tool, we implement three optimizations and heuristics, which achieve better performance on real data, and similar or better performance on simulated data, than state-of-the-art tools Cufflinks, IsoLasso and SLIDE. Our tool, called Traph, is available at http://www.cs.helsinki.fi/gsa/traph/

q-bio.QM