Machine Learning and Integrative Analysis of Biomedical Big Data.

Recent developments in high-throughput technologies have accelerated the accumulation of massive amounts of omics data from multiple sources: genome, epigenome, transcriptome, proteome, metabolome, etc. Traditionally, data from each source (e.g., genome) is analyzed in isolation using statistical and machine learning (ML) methods. Integrative analysis of multi-omics and clinical data is key to new biomedical discoveries and advancements in precision medicine. However, data integration poses new computational challenges as well as exacerbates the ones associated with single-omics studies. Specialized computational approaches are required to effectively and efficiently perform integrative analysis of biomedical data acquired from diverse modalities. In this review, we discuss state-of-the-art ML-based approaches for tackling five specific computational challenges associated with integrative analysis: curse of dimensionality, data heterogeneity, missing data, class imbalance and scalability issues

Оптимизационный подход к выбору методов обнаружения аномалий в однородных текстовых коллекциях

The problem of detecting anomalous documents in text collections is considered. The existing methods for detecting anomalies are not universal and do not show a stable result on different data sets. The accuracy of the results depends on the choice of parameters at each step of the problem solving algorithm process, and for different collections different sets of parameters are optimal. Not all of the existing algorithms for detecting anomalies work effectively with text data, which vector representation is characterized by high dimensionality with strong sparsity. The problem of finding anomalies is considered in the following statement: it is necessary to checking a new document uploaded to an applied intelligent information system for congruence with a homogeneous collection of documents stored in it. In such systems that process legal documents the following limitations are imposed on the anomaly detection methods: high accuracy, computational efficiency, reproducibility of results and explicability of the solution. Methods satisfying these conditions are investigated. The paper examines the possibility of evaluating text documents on the scale of anomaly by deliberately introducing a foreign document into the collection. A strategy for detecting novelty of the document in relation to the collection is proposed, which assumes a reasonable selection of methods and parameters. It is shown how the accuracy of the solution is affected by the choice of vectorization options, tokenization principles, dimensionality reduction methods and parameters of novelty detection algorithms. The experiment was conducted on two homogeneous collections of documents containing technical norms: standards in the field of information technology and railways. The following approaches were used: calculation of the anomaly index as the Hellinger distance between the distributions of the remoteness of documents to the center of the collection and to the foreign document; optimization of the novelty detection algorithms depending on the methods of vectorization and dimensionality reduction. The vector space was constructed using the TF-IDF transformation and ARTM topic modeling. The following algorithms have been tested: Isolation Forest, Local Outlier Factor and One-Class SVM (based on Support Vector Machine). The experiment confirmed the effectiveness of the proposed optimization strategy for determining the appropriate method for detecting anomalies for a given text collection. When searching for an anomaly in the context of topic clustering of legal documents, the Isolating Forest method is proved to be effective. When vectorizing documents using TF-IDF, it is advisable to choose the optimal dictionary parameters and use the One-Class SVM method with the corresponding feature space transformation function.Рассматривается задача обнаружения аномальных документов в текстовых коллекциях. Существующие методы выявления аномалий не универсальны и не показывают стабильный результат на разных наборах данных. Точность результатов зависит от выбора параметров на каждом из шагов алгоритма, и для разных коллекций оптимальны различные наборы параметров. Не все из существующих алгоритмов обнаружения аномалий эффективно работают с текстовыми данными, векторное представление которых характеризуется большой размерностью при сильной разреженности. Задача поиска аномалий рассматривается в следующей постановке: требуется проверить новый документ, загружаемый в прикладную интеллектуальную информационную систему (ПИИС), на соответствие хранящейся в ней однородной коллекции документов. В ПИИС, обрабатывающих юридически значимые документы, на методы обнаружения аномалий накладываются следующие ограничения: высокая точность, вычислительная эффективность, воспроизводимость результатов, а также объяснимость решения. Исследуются методы, удовлетворяющие этим условиям. В работе изучается возможность оценки текстовых документов по шкале аномальности путем внедрения в коллекцию заведомо инородного документа. Предложена стратегия обнаружения в документе новизны по отношению к коллекции, предполагающая обоснованный подбор методов и параметров. Показано, как на точность решения влияет выбор вариантов векторизации, принципов токенизации, методов снижения размерности и параметров алгоритмов поиска аномалий. Эксперимент проведен на двух однородных коллекциях нормативно-технических документов: стандартов в отношении информационных технологий и в сфере железных дорог. Использовались подходы: вычисление индекса аномальности как расстояния Хеллингера между распределениями близости документов к центру коллекции и к инородному документу; оптимизация алгоритмов поиска аномалий в зависимости от методов векторизации и снижения размерности. Векторное пространство строилось с помощью преобразования TF-IDF и тематического моделирования ARTM. Тестировались алгоритмы Isolation Forest (изолирующий лес), Local Outlier Factor (локальный фактор выброса), OneClass SVM (вариант метода опорных векторов). Эксперимент подтвердил эффективность предложенной оптимизационной стратегии для определения подходящего метода обнаружения аномалий для заданной текстовой коллекции. При поиске аномалии в рамках тематической кластеризации юридически значимых документов эффективен метод изолирующего леса. При векторизации документов по TF-IDF целесообразно подобрать оптимальные параметры словаря и использовать метод опорных векторов с соответствующей функцией преобразования признакового пространства

Bioinformatics applied to human genomics and proteomics: development of algorithms and methods for the discovery of molecular signatures derived from omic data and for the construction of co-expression and interaction networks

[EN] The present PhD dissertation develops and applies Bioinformatic methods and tools to address key current problems in the analysis of human omic data. This PhD has been organised by main objectives into four different chapters focused on: (i) development of an algorithm for the analysis of changes and heterogeneity in large-scale omic data; (ii) development of a method for non-parametric feature selection; (iii) integration and analysis of human protein-protein interaction networks and (iv) integration and analysis of human co-expression networks derived from tissue expression data and evolutionary profiles of proteins. In the first chapter, we developed and tested a new robust algorithm in R, called DECO, for the discovery of subgroups of features and samples within large-scale omic datasets, exploring all feature differences possible heterogeneity, through the integration of both data dispersion and predictor-response information in a new statistic parameter called h (heterogeneity score). In the second chapter, we present a simple non-parametric statistic to measure the cohesiveness of categorical variables along any quantitative variable, applicable to feature selection in all types of big data sets. In the third chapter, we describe an analysis of the human interactome integrating two global datasets from high-quality proteomics technologies: HuRI (a human protein-protein interaction network generated by a systematic experimental screening based on Yeast-Two-Hybrid technology) and Cell-Atlas (a comprehensive map of subcellular localization of human proteins generated by antibody imaging). This analysis aims to create a framework for the subcellular localization characterization supported by the human protein-protein interactome. In the fourth chapter, we developed a full integration of three high-quality proteome-wide resources (Human Protein Atlas, OMA and TimeTree) to generate a robust human co-expression network across tissues assigning each human protein along the evolutionary timeline. In this way, we investigate how old in evolution and how correlated are the different human proteins, and we place all them in a common interaction network. As main general comment, all the work presented in this PhD uses and develops a wide variety of bioinformatic and statistical tools for the analysis, integration and enlighten of molecular signatures and biological networks using human omic data. Most of this data corresponds to sample cohorts generated in recent biomedical studies on specific human diseases