Structural Alignment of RNAs Using Profile-csHMMs and Its Application to RNA Homology Search: Overview and New Results

Systematic research on noncoding RNAs (ncRNAs) has revealed that many ncRNAs are actively involved in various biological networks. Therefore, in order to fully understand the mechanisms of these networks, it is crucial to understand the roles of ncRNAs. Unfortunately, the annotation of ncRNA genes that give rise to functional RNA molecules has begun only recently, and it is far from being complete. Considering the huge amount of genome sequence data, we need efficient computational methods for finding ncRNA genes. One effective way of finding ncRNA genes is to look for regions that are similar to known ncRNA genes. As many ncRNAs have well-conserved secondary structures, we need statistical models that can represent such structures for this purpose. In this paper, we propose a new method for representing RNA sequence profiles and finding structural alignment of RNAs based on profile context-sensitive hidden Markov models (profile-csHMMs). Unlike existing models, the proposed approach can handle any kind of RNA secondary structures, including pseudoknots. We show that profile-csHMMs can provide an effective framework for the computational analysis of RNAs and the identification of ncRNA genes

Efficient Identification of Equivalences in Dynamic Graphs and Pedigree Structures

We propose a new framework for designing test and query functions for complex structures that vary across a given parameter such as genetic marker position. The operations we are interested in include equality testing, set operations, isolating unique states, duplication counting, or finding equivalence classes under identifiability constraints. A motivating application is locating equivalence classes in identity-by-descent (IBD) graphs, graph structures in pedigree analysis that change over genetic marker location. The nodes of these graphs are unlabeled and identified only by their connecting edges, a constraint easily handled by our approach. The general framework introduced is powerful enough to build a range of testing functions for IBD graphs, dynamic populations, and other structures using a minimal set of operations. The theoretical and algorithmic properties of our approach are analyzed and proved. Computational results on several simulations demonstrate the effectiveness of our approach.Comment: Code for paper available at http://www.stat.washington.edu/~hoytak/code/hashreduc

A study of hierarchical and flat classification of proteins

Automatic classification of proteins using machine learning is an important problem that has received significant attention in the literature. One feature of this problem is that expert-defined hierarchies of protein classes exist and can potentially be exploited to improve classification performance. In this article we investigate empirically whether this is the case for two such hierarchies. We compare multi-class classification techniques that exploit the information in those class hierarchies and those that do not, using logistic regression, decision trees, bagged decision trees, and support vector machines as the underlying base learners. In particular, we compare hierarchical and flat variants of ensembles of nested dichotomies. The latter have been shown to deliver strong classification performance in multi-class settings. We present experimental results for synthetic, fold recognition, enzyme classification, and remote homology detection data. Our results show that exploiting the class hierarchy improves performance on the synthetic data, but not in the case of the protein classification problems. Based on this we recommend that strong flat multi-class methods be used as a baseline to establish the benefit of exploiting class hierarchies in this area

Conformal Frequency Estimation with Sketched Data under Relaxed Exchangeability

A flexible method is developed to construct a confidence interval for the frequency of a queried object in a very large data set, based on a much smaller sketch of the data. The approach requires no knowledge of the data distribution or of the details of the sketching algorithm; instead, it constructs provably valid frequentist confidence intervals for random queries using a conformal inference approach. After achieving marginal coverage for random queries under the assumption of data exchangeability, the proposed method is extended to provide stronger inferences accounting for possibly heterogeneous frequencies of different random queries, redundant queries, and distribution shifts. While the presented methods are broadly applicable, this paper focuses on use cases involving the count-min sketch algorithm and a non-linear variation thereof, to facilitate comparison to prior work. In particular, the developed methods are compared empirically to frequentist and Bayesian alternatives, through simulations and experiments with data sets of SARS-CoV-2 DNA sequences and classic English literature.Comment: 56 pages, 31 figures, 2 tables. arXiv admin note: substantial text overlap with arXiv:2204.0427

Tradeoffs for nearest neighbors on the sphere

We consider tradeoffs between the query and update complexities for the (approximate) nearest neighbor problem on the sphere, extending the recent spherical filters to sparse regimes and generalizing the scheme and analysis to account for different tradeoffs. In a nutshell, for the sparse regime the tradeoff between the query complexity $n^{\rho_q}$ and update complexity $n^{\rho_u}$ for data sets of size $n$ is given by the following equation in terms of the approximation factor $c$ and the exponents $\rho_q$ and $\rho_u$: $$c^2\sqrt{\rho_q}+(c^2-1)\sqrt{\rho_u}=\sqrt{2c^2-1}.$$ For small $c=1+\epsilon$, minimizing the time for updates leads to a linear space complexity at the cost of a query time complexity $n^{1-4\epsilon^2}$. Balancing the query and update costs leads to optimal complexities $n^{1/(2c^2-1)}$, matching bounds from [Andoni-Razenshteyn, 2015] and [Dubiner, IEEE-TIT'10] and matching the asymptotic complexities of [Andoni-Razenshteyn, STOC'15] and [Andoni-Indyk-Laarhoven-Razenshteyn-Schmidt, NIPS'15]. A subpolynomial query time complexity $n^{o(1)}$ can be achieved at the cost of a space complexity of the order $n^{1/(4\epsilon^2)}$, matching the bound $n^{\Omega(1/\epsilon^2)}$ of [Andoni-Indyk-Patrascu, FOCS'06] and [Panigrahy-Talwar-Wieder, FOCS'10] and improving upon results of [Indyk-Motwani, STOC'98] and [Kushilevitz-Ostrovsky-Rabani, STOC'98]. For large $c$, minimizing the update complexity results in a query complexity of $n^{2/c^2+O(1/c^4)}$, improving upon the related exponent for large $c$ of [Kapralov, PODS'15] by a factor $2$, and matching the bound $n^{\Omega(1/c^2)}$ of [Panigrahy-Talwar-Wieder, FOCS'08]. Balancing the costs leads to optimal complexities $n^{1/(2c^2-1)}$, while a minimum query time complexity can be achieved with update complexity $n^{2/c^2+O(1/c^4)}$, improving upon the previous best exponents of Kapralov by a factor $2$.Comment: 16 pages, 1 table, 2 figures. Mostly subsumed by arXiv:1608.03580 [cs.DS] (along with arXiv:1605.02701 [cs.DS]

Four Lessons in Versatility or How Query Languages Adapt to the Web

Exposing not only human-centered information, but machine-processable data on the Web is one of the commonalities of recent Web trends. It has enabled a new kind of applications and businesses where the data is used in ways not foreseen by the data providers. Yet this exposition has fractured the Web into islands of data, each in different Web formats: Some providers choose XML, others RDF, again others JSON or OWL, for their data, even in similar domains. This fracturing stifles innovation as application builders have to cope not only with one Web stack (e.g., XML technology) but with several ones, each of considerable complexity. With Xcerpt we have developed a rule- and pattern based query language that aims to give shield application builders from much of this complexity: In a single query language XML and RDF data can be accessed, processed, combined, and re-published. Though the need for combined access to XML and RDF data has been recognized in previous work (including the W3C’s GRDDL), our approach differs in four main aspects: (1) We provide a single language (rather than two separate or embedded languages), thus minimizing the conceptual overhead of dealing with disparate data formats. (2) Both the declarative (logic-based) and the operational semantics are unified in that they apply for querying XML and RDF in the same way. (3) We show that the resulting query language can be implemented reusing traditional database technology, if desirable. Nevertheless, we also give a unified evaluation approach based on interval labelings of graphs that is at least as fast as existing approaches for tree-shaped XML data, yet provides linear time and space querying also for many RDF graphs. We believe that Web query languages are the right tool for declarative data access in Web applications and that Xcerpt is a significant step towards a more convenient, yet highly efficient data access in a “Web of Data”