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

Systems Analytics and Integration of Big Omics Data

A “genotype"" is essentially an organism's full hereditary information which is obtained from its parents. A ""phenotype"" is an organism's actual observed physical and behavioral properties. These may include traits such as morphology, size, height, eye color, metabolism, etc. One of the pressing challenges in computational and systems biology is genotype-to-phenotype prediction. This is challenging given the amount of data generated by modern Omics technologies. This “Big Data” is so large and complex that traditional data processing applications are not up to the task. Challenges arise in collection, analysis, mining, sharing, transfer, visualization, archiving, and integration of these data. In this Special Issue, there is a focus on the systems-level analysis of Omics data, recent developments in gene ontology annotation, and advances in biological pathways and network biology. The integration of Omics data with clinical and biomedical data using machine learning is explored. This Special Issue covers new methodologies in the context of gene–environment interactions, tissue-specific gene expression, and how external factors or host genetics impact the microbiome

Integrative bioinformatics and graph-based methods for predicting adverse effects of developmental drugs

Adverse drug effects are complex phenomena that involve the interplay between drug molecules and their protein targets at various levels of biological organisation, from molecular to organismal. Many factors are known to contribute toward the safety profile of a drug, including the chemical properties of the drug molecule itself, the biological properties of drug targets and other proteins that are involved in pharmacodynamics and pharmacokinetics aspects of drug action, and the characteristics of the intended patient population. A multitude of scattered publicly available resources exist that cover these important aspects of drug activity. These include manually curated biological databases, high-throughput experimental results from gene expression and human genetics resources as well as drug labels and registered clinical trial records. This thesis proposes an integrated analysis of these disparate sources of information to help bridge the gap between the molecular and the clinical aspects of drug action. For example, to address the commonly held assumption that narrowly expressed proteins make safer drug targets, an integrative data-driven analysis was conducted to systematically investigate the relationship between the tissue expression profile of drug targets and the organs affected by clinically observed adverse drug reactions. Similarly, human genetics data were used extensively throughout the thesis to compare adverse symptoms induced by drug molecules with the phenotypes associated with the genes encoding their target proteins. One of the main outcomes of this thesis was the generation of a large knowledge graph, which incorporates diverse molecular and phenotypic data in a structured network format. To leverage the integrated information, two graph-based machine learning methods were developed to predict a wide range of adverse drug effects caused by approved and developmental therapies

Towards Name Disambiguation: Relational, Streaming, and Privacy-Preserving Text Data

In the real world, our DNA is unique but many people share names. This phenomenon often causes erroneous aggregation of documents of multiple persons who are namesakes of one another. Such mistakes deteriorate the performance of document retrieval, web search, and more seriously, cause improper attribution of credit or blame in digital forensics. To resolve this issue, the name disambiguation task 1 is designed to partition the documents associated with a name reference such that each partition contains documents pertaining to a unique real-life person. Existing algorithms for this task mainly suffer from the following drawbacks. First, the majority of existing solutions substantially rely on feature engineering, such as biographical feature extraction, or construction of auxiliary features from Wikipedia. However, for many scenarios, such features may be costly to obtain or unavailable in privacy sensitive domains. Instead we solve the name disambiguation task in restricted setting by leveraging only the relational data in the form of anonymized graphs. Second, most of the existing works for this task operate in a batch mode, where all records to be disambiguated are initially available to the algorithm. However, more realistic settings require that the name disambiguation task should be performed in an online streaming fashion in order to identify records of new ambiguous entities having no preexisting records. Finally, we investigate the potential disclosure risk of textual features used in name disambiguation and propose several algorithms to tackle the task in a privacy-aware scenario. In summary, in this dissertation, we present a number of novel approaches to address name disambiguation tasks from the above three aspects independently, namely relational, streaming, and privacy preserving textual data

Implementazione ed ottimizzazione di algoritmi per l'analisi di Biomedical Big Data

Big Data Analytics poses many challenges to the research community who has to handle several computational problems related to the vast amount of data. An increasing interest involves Biomedical data, aiming to get the so-called personalized medicine, where therapy plans are designed on the specific genotype and phenotype of an individual patient and algorithm optimization plays a key role to this purpose. In this work we discuss about several topics related to Biomedical Big Data Analytics, with a special attention to numerical issues and algorithmic solutions related to them. We introduce a novel feature selection algorithm tailored on omics datasets, proving its efficiency on synthetic and real high-throughput genomic datasets. We tested our algorithm against other state-of-art methods obtaining better or comparable results. We also implemented and optimized different types of deep learning models, testing their efficiency on biomedical image processing tasks. Three novel frameworks for deep learning neural network models development are discussed and used to describe the numerical improvements proposed on various topics. In the first implementation we optimize two Super Resolution models showing their results on NMR images and proving their efficiency in generalization tasks without a retraining. The second optimization involves a state-of-art Object Detection neural network architecture, obtaining a significant speedup in computational performance. In the third application we discuss about femur head segmentation problem on CT images using deep learning algorithms. The last section of this work involves the implementation of a novel biomedical database obtained by the harmonization of multiple data sources, that provides network-like relationships between biomedical entities. Data related to diseases and other biological relates were mined using web-scraping methods and a novel natural language processing pipeline was designed to maximize the overlap between the different data sources involved in this project

Pacific Symposium on Biocomputing 2023

The Pacific Symposium on Biocomputing (PSB) 2023 is an international, multidisciplinary conference for the presentation and discussion of current research in the theory and application of computational methods in problems of biological significance. Presentations are rigorously peer reviewed and are published in an archival proceedings volume. PSB 2023 will be held on January 3-7, 2023 in Kohala Coast, Hawaii. Tutorials and workshops will be offered prior to the start of the conference.PSB 2023 will bring together top researchers from the US, the Asian Pacific nations, and around the world to exchange research results and address open issues in all aspects of computational biology. It is a forum for the presentation of work in databases, algorithms, interfaces, visualization, modeling, and other computational methods, as applied to biological problems, with emphasis on applications in data-rich areas of molecular biology.The PSB has been designed to be responsive to the need for critical mass in sub-disciplines within biocomputing. For that reason, it is the only meeting whose sessions are defined dynamically each year in response to specific proposals. PSB sessions are organized by leaders of research in biocomputing's 'hot topics.' In this way, the meeting provides an early forum for serious examination of emerging methods and approaches in this rapidly changing field

Advances in decomposing complex metabolite mixtures using substructure- and network-based computational metabolomics approaches

Covering: up to the end of 2020 Recently introduced computational metabolome mining tools have started to positively impact the chemical and biological interpretation of untargeted metabolomics analyses. We believe that these current advances make it possible to start decomposing complex metabolite mixtures into substructure and chemical class information, thereby supporting pivotal tasks in metabolomics analysis including metabolite annotation, the comparison of metabolic profiles, and network analyses. In this review, we highlight and explain key tools and emerging strategies covering 2015 up to the end of 2020. The majority of these tools aim at processing and analyzing liquid chromatography coupled to mass spectrometry fragmentation data. We start with defining what substructures are, how they relate to molecular fingerprints, and how recognizing them helps to decompose complex mixtures. We continue with chemical classes that are based on the presence or absence of particular molecular scaffolds and/or functional groups and are thus intrinsically related to substructures. We discuss novel tools to mine substructures, annotate chemical compound classes, and create mass spectral networks from metabolomics data and demonstrate them using two case studies. We also review and speculate about the opportunities that NMR spectroscopy-based metabolome mining of complex metabolite mixtures offers to discover substructures and chemical classes. Finally, we will describe the main benefits and limitations of the current tools and strategies that rely on them, and our vision on how this exciting field can develop toward repository-scale-sized metabolomics analyses. Complementary sources of structural information from genomics analyses and well-curated taxonomic records are also discussed. Many research fields such as natural products discovery, pharmacokinetic and drug metabolism studies, and environmental metabolomics increasingly rely on untargeted metabolomics to gain biochemical and biological insights. The here described technical advances will benefit all those metabolomics disciplines by transforming spectral data into knowledge that can answer biological questions