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Bait enrichment is a protocol that is becoming increasingly ubiquitous as it has been shown to successfully amplify regions of interest in metagenomic samples. In this method, a set of synthetic probes (‘baits’) are designed, manufactured and applied to fragmented metagenomic DNA. The probes bind to the fragmented DNA and any unbound DNA is rinsed away, leaving the bound fragments to be amplified for sequencing. Metsky et al. demonstrated that bait-enrichment is capable of detecting a large number of human viral pathogens within metagenomic samples.

We formalize the problem of designing baits by defining the Minimum Bait Cover problem, show that the problem is NP-hard even under very restrictive assumptions, and design an efficient heuristic that takes advantage of succinct data structures. We refer to our method as Syotti. The running time of Syotti shows linear scaling in practice, running at least an order of magnitude faster than state-of-the-art methods, including the method of Metsky et al. At the same time, our method produces bait sets that are smaller than the ones produced by the competing methods, while also leaving fewer positions uncovered. Lastly, we show that Syotti requires only 25 min to design baits for a dataset comprised of 3 billion nucleotides from 1000 related bacterial substrains, whereas the method of Metsky et al. shows clearly super-linear running time and fails to process even a subset of 17% of the data in 72 h.

https://github.com/jnalanko/syotti.

Supplementary data are available at Bioinformatics online.

 

We present approximation and exact algorithms for piecewise regression of univariate and bivariate data using fixed-degree polynomials. Specifically, given a set S of n data points (x1, y1), . . . , (xn, yn) ∈ Rd × R where d ∈ {1, 2}, the goal is to segment xi’s into some (arbitrary) number of disjoint pieces P1, . . . , Pk, where each piece Pj is associated with a fixed-degree polynomial fj : Rd → R, to minimize the total loss function λk+􏰄ni=1(yi −f(xi))2, where λ ≥ 0 is a regularization term that penalizes model complexity (number of pieces) and f : 􏰇kj=1 Pj → R is the piecewise polynomial function defined as f|Pj = fj. The pieces P1,...,Pk are disjoint intervals of R in the case of univariate data and disjoint axis-aligned rectangles in the case of bivariate data. Our error approximation allows use of any fixed-degree polynomial, not just linear functions. Our main results are the following. For univariate data, we present a (1 + ε)-approximation algorithm with time complexity O(nε log1ε), assuming that data is presented in sorted order of xi’s. For bivariate data, we √ present three results: a sub-exponential exact algorithm with running time nO( n); a polynomial-time constant- approximation algorithm; and a quasi-polynomial time approximation scheme (QPTAS). The bivariate case is believed to be NP-hard in the folklore but we could not find a published record in the literature, so in this paper we also present a hardness proof for completeness. 

In its most traditional setting, the main concern of optimization theory is the search for optimal solutions for instances of a given computational problem. A recent trend of research in artificial intelligence, called solution diversity, has focused on the development of notions of optimality that may be more appropriate in settings where subjectivity is essential. The idea is that instead of aiming at the development of algorithms that output a single optimal solution, the goal is to investigate algorithms that output a small set of sufficiently good solutions that are sufficiently diverse from one another. In this way, the user has the opportunity to choose the solution that is most appropriate to the context at hand. It also displays the richness of the solution space.When combined with techniques from parameterized complexity theory, the paradigm of diversity of solutions offers a powerful algorithmic framework to address problems of practical relevance. In this work, we investigate the impact of this combination in the field of Kemeny Rank Aggregation, a well-studied class of problems lying in the intersection of order theory and social choice theory and also in the field of order theory itself. In particular, we show that KRA is fixed-parameter tractable with respect to natural parameters providing natural formalizations of the notions of diversity and of the notion of a sufficiently good solution. Our main results work both when considering the traditional setting of aggregation over linearly ordered votes, and in the more general setting where votes are partially ordered.<