Grammatical inference of directed acyclic graph languages with polynomial time complexity

[EN] In this paper we study the learning of graph languages. We extend the well-known classes of k-testability and k-testability in the strict sense languages to directed graph languages. We propose a grammatical inference algorithm to learn the class of directed acyclic k- testable in the strict sense graph languages. The algorithm runs in polynomial time and identifies this class of languages from positive data. We study its efficiency under several criteria, and perform a comprehensive experimentation with four datasets to show the validity of the method. Many fields, from pattern recognition to data compression, can take advantage of these results.Gallego, A.; López Rodríguez, D.; Calera-Rubio, J. (2018). Grammatical inference of directed acyclic graph languages with polynomial time complexity. Journal of Computer and System Sciences. 95:19-34. https://doi.org/10.1016/j.jcss.2017.12.002S19349

Identifying Novel Drug Indications through Automated Reasoning

abstract: Background With the large amount of pharmacological and biological knowledge available in literature, finding novel drug indications for existing drugs using in silico approaches has become increasingly feasible. Typical literature-based approaches generate new hypotheses in the form of protein-protein interactions networks by means of linking concepts based on their cooccurrences within abstracts. However, this kind of approaches tends to generate too many hypotheses, and identifying new drug indications from large networks can be a time-consuming process. Methodology In this work, we developed a method that acquires the necessary facts from literature and knowledge bases, and identifies new drug indications through automated reasoning. This is achieved by encoding the molecular effects caused by drug-target interactions and links to various diseases and drug mechanism as domain knowledge in AnsProlog, a declarative language that is useful for automated reasoning, including reasoning with incomplete information. Unlike other literature-based approaches, our approach is more fine-grained, especially in identifying indirect relationships for drug indications. Conclusion/Significance To evaluate the capability of our approach in inferring novel drug indications, we applied our method to 943 drugs from DrugBank and asked if any of these drugs have potential anti-cancer activities based on information on their targets and molecular interaction types alone. A total of 507 drugs were found to have the potential to be used for cancer treatments. Among the potential anti-cancer drugs, 67 out of 81 drugs (a recall of 82.7%) are indeed known cancer drugs. In addition, 144 out of 289 drugs (a recall of 49.8%) are non-cancer drugs that are currently tested in clinical trials for cancer treatments. These results suggest that our method is able to infer drug indications (original or alternative) based on their molecular targets and interactions alone and has the potential to discover novel drug indications for existing drugs.The article is published at http://journals.plos.org/plosone/article?id=10.1371/journal.pone.004094

Modelling epistasis in genetic disease using Petri nets, evolutionary computation and frequent itemset mining

Petri nets are useful for mathematically modelling disease-causing genetic epistasis. A Petri net model of an interaction has the potential to lead to biological insight into the cause of a genetic disease. However, defining a Petri net by hand for a particular interaction is extremely difficult because of the sheer complexity of the problem and degrees of freedom inherent in a Petri net’s architecture. We propose therefore a novel method, based on evolutionary computation and data mining, for automatically constructing Petri net models of non-linear gene interactions. The method comprises two main steps. Firstly, an initial partial Petri net is set up with several repeated sub-nets that model individual genes and a set of constraints, comprising relevant common sense and biological knowledge, is also defined. These constraints characterise the class of Petri nets that are desired. Secondly, this initial Petri net structure and the constraints are used as the input to a genetic algorithm. The genetic algorithm searches for a Petri net architecture that is both a superset of the initial net, and also conforms to all of the given constraints. The genetic algorithm evaluation function that we employ gives equal weighting to both the accuracy of the net and also its parsimony. We demonstrate our method using an epistatic model related to the presence of digital ulcers in systemic sclerosis patients that was recently reported in the literature. Our results show that although individual “perfect” Petri nets can frequently be discovered for this interaction, the true value of this approach lies in generating many different perfect nets, and applying data mining techniques to them in order to elucidate common and statistically significant patterns of interaction

Grammatical inference with bioinformatics criteria

In this paper we describe both the theoretical and practical results of a novel approach that combines hybrid techniques of association analysis and classical sequentiation algorithms of genomics to generate the grammatical structures of a specific language. We used an application of a compiler generator system that allows a practical application to be developed within the area of grammarware, where the concepts of language analysis are applied to other disciplines, such as bioinformatics. The tool allows the complexity of the obtained grammar to be measured automatically from textual data. A technique involving the incremental discovery of sequential patterns is presented to obtain simplified production rules, and compacted with bioinformatics criteria to make up a grammar

A Relevance Feedback-Based System For Quickly Narrowing Biomedical Literature Search Result

The online literature is an important source that helps people find the information. The quick increase of online literature makes the manual search process for the most relevant information a very time-consuming task and leads to sifting through many results to find the relevant ones. The existing search engines and online databases return a list of results that satisfy the user\u27s search criteria. The list is often too long for the user to go through every hit if he/she does not exactly know what he/she wants or/and does not have time to review them one by one. My focus is on how to find biomedical literature in a fastest way. In this dissertation, I developed a biomedical literature search system that uses relevance feedback mechanism, fuzzy logic, text mining techniques and Unified Medical Language System. The system extracts and decodes information from the online biomedical documents and uses the extracted information to first filter unwanted documents and then ranks the related ones based on the user preferences. I used text mining techniques to extract PDF document features and used these features to filter unwanted documents with the help of fuzzy logic. The system extracts meaning and semantic relations between texts and calculates the similarity between documents using these relations. Moreover, I developed a fuzzy literature ranking method that uses fuzzy logic, text mining techniques and Unified Medical Language System. The ranking process is utilized based on fuzzy logic and Unified Medical Language System knowledge resources. The fuzzy ranking method uses semantic type and meaning concepts to map the relations between texts in documents. The relevance feedback-based biomedical literature search system is evaluated using a real biomedical data that created using dobutamine (drug name). The data set contains 1,099 original documents. To obtain coherent and reliable evaluation results, two physicians are involved in the system evaluation. Using (30-day mortality) as specific query, the retrieved result precision improves by 87.7% in three rounds, which shows the effectiveness of using relevance feedback, fuzzy logic and UMLS in the search process. Moreover, the fuzzy-based ranking method is evaluated in term of ranking the biomedical search result. Experiments show that the fuzzy-based ranking method improves the average ranking order accuracy by 3.35% and 29.55% as compared with UMLS meaning and semantic type methods respectively

Linguistically inspired roadmap for building biologically reliable protein language models

Deep neural-network-based language models (LMs) are increasingly applied to large-scale protein sequence data to predict protein function. However, being largely black-box models and thus challenging to interpret, current protein LM approaches do not contribute to a fundamental understanding of sequence-function mappings, hindering rule-based biotherapeutic drug development. We argue that guidance drawn from linguistics, a field specialized in analytical rule extraction from natural language data, can aid with building more interpretable protein LMs that are more likely to learn relevant domain-specific rules. Differences between protein sequence data and linguistic sequence data require the integration of more domain-specific knowledge in protein LMs compared to natural language LMs. Here, we provide a linguistics-based roadmap for protein LM pipeline choices with regard to training data, tokenization, token embedding, sequence embedding, and model interpretation. Incorporating linguistic ideas into protein LMs enables the development of next-generation interpretable machine-learning models with the potential of uncovering the biological mechanisms underlying sequence-function relationships.Comment: 27 pages, 4 figure

Evaluation of Existing Methods for High-Order Epistasis Detection

[Abstract] Finding epistatic interactions among loci when expressing a phenotype is a widely employed strategy to understand the genetic architecture of complex traits in GWAS. The abundance of methods dedicated to the same purpose, however, makes it increasingly difficult for scientists to decide which method is more suitable for their studies. This work compares the different epistasis detection methods published during the last decade in terms of runtime, detection power and type I error rate, with a special emphasis on high-order interactions. Results show that in terms of detection power, the only methods that perform well across all experiments are the exhaustive methods, although their computational cost may be prohibitive in large-scale studies. Regarding non-exhaustive methods, not one could consistently find epistasis interactions when marginal effects are absent. If marginal effects are present, there are methods that perform well for high-order interactions, such as BADTrees, FDHE-IW, SingleMI or SNPHarvester. As for false-positive control, only SNPHarvester, FDHE-IW and DCHE show good results. The study concludes that there is no single epistasis detection method to recommend in all scenarios. Authors should prioritize exhaustive methods when sufficient computational resources are available considering the data set size, and resort to non-exhaustive methods when the analysis time is prohibitive.10.13039/501100010801-Xunta de Galicia (Grant Number: ED431C2016-037, ED431C2017/04 and ED431G2019/01) 10.13039/501100003176-Ministerio de Educacion Cultura y Deporte (Grant Number: FPU16/01333) 10.13039/501100003329-Ministerio de Economia y Competitividad (Grant Number: CGL2016-75482-P, PID2019-104184RB-I00, AEI/FEDER/EU, 10.13039/50110 and TIN2016-75845-P)Xunta de Galicia; ED431C2016-037Xunta de Galicia; ED431G2019/01Xunta de Galicia; ED431C 2017/0

Automatic reconstruction of a bacterial regulatory network using Natural Language Processing

<p>Abstract</p> <p>Background</p> <p>Manual curation of biological databases, an expensive and labor-intensive process, is essential for high quality integrated data. In this paper we report the implementation of a state-of-the-art Natural Language Processing system that creates computer-readable networks of regulatory interactions directly from different collections of abstracts and full-text papers. Our major aim is to understand how automatic annotation using Text-Mining techniques can complement manual curation of biological databases. We implemented a rule-based system to generate networks from different sets of documents dealing with regulation in <it>Escherichia coli </it>K-12.</p> <p>Results</p> <p>Performance evaluation is based on the most comprehensive transcriptional regulation database for any organism, the manually-curated RegulonDB, 45% of which we were able to recreate automatically. From our automated analysis we were also able to find some new interactions from papers not already curated, or that were missed in the manual filtering and review of the literature. We also put forward a novel Regulatory Interaction Markup Language better suited than SBML for simultaneously representing data of interest for biologists and text miners.</p> <p>Conclusion</p> <p>Manual curation of the output of automatic processing of text is a good way to complement a more detailed review of the literature, either for validating the results of what has been already annotated, or for discovering facts and information that might have been overlooked at the triage or curation stages.</p