Parameterized Algorithms for String Matching to DAGs: Funnels and Beyond

The problem of String Matching to Labeled Graphs (SMLG) asks to find all the paths in a labeled graph G = (V, E) whose spellings match that of an input string S ? ?^m. SMLG can be solved in quadratic O(m|E|) time [Amir et al., JALG 2000], which was proven to be optimal by a recent lower bound conditioned on SETH [Equi et al., ICALP 2019]. The lower bound states that no strongly subquadratic time algorithm exists, even if restricted to directed acyclic graphs (DAGs). In this work we present the first parameterized algorithms for SMLG on DAGs. Our parameters capture the topological structure of G. All our results are derived from a generalization of the Knuth-Morris-Pratt algorithm [Park and Kim, CPM 1995] optimized to work in time proportional to the number of prefix-incomparable matches. To obtain the parameterization in the topological structure of G, we first study a special class of DAGs called funnels [Millani et al., JCO 2020] and generalize them to k-funnels and the class ST_k. We present several novel characterizations and algorithmic contributions on both funnels and their generalizations

Improving RNA Assembly via Safety and Completeness in Flow Decompositions

Extended version of RECOMB 2022 paperDecomposing a network flow into weighted paths is a problem with numerous applications, ranging from networking, transportation planning, to bioinformatics. In some applications we look for a decomposition that is optimal with respect to some property, such as the number of paths used, robustness to edge deletion, or length of the longest path. However, in many bioinformatic applications, we seek a specific decomposition where the paths correspond to some underlying data that generated the flow. In these cases, no optimization criteria guarantee the identification of the correct decomposition. Therefore, we propose to instead report the safe paths, which are subpaths of at least one path in every flow decomposition. In this work, we give the first local characterization of safe paths for flow decompositions in directed acyclic graphs, leading to a practical algorithm for finding the complete set of safe paths. In addition, we evaluate our algorithm on RNA transcript data sets against a trivial safe algorithm (extended unitigs), the recently proposed safe paths for path covers (TCBB 2021) and the popular heuristic greedy-width. On the one hand, we found that besides maintaining perfect precision, our safe and complete algorithm reports a significantly higher coverage (≈50 compared with the other safe algorithms. On the other hand, the greedy-width algorithm although reporting a better coverage, it also reports a significantly lower precision on complex graphs (for genes expressing a large number of transcripts). Overall, our safe and complete algorithm outperforms (by ≈20 greedy-width on a unified metric (F-score) considering both coverage and precision when the evaluated data set has a significant number of complex graphs. Moreover, it also has a superior time (4−5×) and space performance (1.2−2.2×), resulting in a better and more practical approach for bioinformatic applications of flow decomposition.Peer reviewe

LIPIcs, Volume 274, ESA 2023, Complete Volume

LIPIcs, Volume 274, ESA 2023, Complete Volum

LIPIcs, Volume 244, ESA 2022, Complete Volume

LIPIcs, Volume 244, ESA 2022, Complete Volum

Ultrasensitive detection of toxocara canis excretory-secretory antigens by a nanobody electrochemical magnetosensor assay.

peer reviewedHuman Toxocariasis (HT) is a zoonotic disease caused by the migration of the larval stage of the roundworm Toxocara canis in the human host. Despite of being the most cosmopolitan helminthiasis worldwide, its diagnosis is elusive. Currently, the detection of specific immunoglobulins IgG against the Toxocara Excretory-Secretory Antigens (TES), combined with clinical and epidemiological criteria is the only strategy to diagnose HT. Cross-reactivity with other parasites and the inability to distinguish between past and active infections are the main limitations of this approach. Here, we present a sensitive and specific novel strategy to detect and quantify TES, aiming to identify active cases of HT. High specificity is achieved by making use of nanobodies (Nbs), recombinant single variable domain antibodies obtained from camelids, that due to their small molecular size (15kDa) can recognize hidden epitopes not accessible to conventional antibodies. High sensitivity is attained by the design of an electrochemical magnetosensor with an amperometric readout with all components of the assay mixed in one single step. Through this strategy, 10-fold higher sensitivity than a conventional sandwich ELISA was achieved. The assay reached a limit of detection of 2 and15 pg/ml in PBST20 0.05% or serum, spiked with TES, respectively. These limits of detection are sufficient to detect clinically relevant toxocaral infections. Furthermore, our nanobodies showed no cross-reactivity with antigens from Ascaris lumbricoides or Ascaris suum. This is to our knowledge, the most sensitive method to detect and quantify TES so far, and has great potential to significantly improve diagnosis of HT. Moreover, the characteristics of our electrochemical assay are promising for the development of point of care diagnostic systems using nanobodies as a versatile and innovative alternative to antibodies. The next step will be the validation of the assay in clinical and epidemiological contexts