Self-adaptive GA, quantitative semantic similarity measures and ontology-based text clustering

As the common clustering algorithms use vector space model (VSM) to represent document, the conceptual relationships between related terms which do not co-occur literally are ignored. A genetic algorithm-based clustering technique, named GA clustering, in conjunction with ontology is proposed in this article to overcome this problem. In general, the ontology measures can be partitioned into two categories: thesaurus-based methods and corpus-based methods. We take advantage of the hierarchical structure and the broad coverage taxonomy of Wordnet as the thesaurus-based ontology. However, the corpus-based method is rather complicated to handle in practical application. We propose a transformed latent semantic analysis (LSA) model as the corpus-based method in this paper. Moreover, two hybrid strategies, the combinations of the various similarity measures, are implemented in the clustering experiments. The results show that our GA clustering algorithm, in conjunction with the thesaurus-based and the LSA-based method, apparently outperforms that with other similarity measures. Moreover, the superiority of the GA clustering algorithm proposed over the commonly used k-means algorithm and the standard GA is demonstrated by the improvements of the clustering performance

Computational analysis on the effects of variations in T and B cells. Primary immunodeficiencies and cancer neoepitopes

Computational approaches are essential to study the effects of inborn and somatic variations. Results from such studies contribute to better diagnosis and therapies. Primary immunodeficiencies (PIDs) are rare inborn defects of key immune response genes. Somatic variations are main drivers of most cancers. Large and diverse data on PID genes and proteins can enable systems biology studies on their dynamic effects on T and B cells. Amino acid substitutions (AASs) are somatic variations that drive cancers. However, AASs also cause cancer-associated antigens that are recognized by lymphocytes as non-self, and are called neoantigens. Detail analysis these neoantigens can be performed due to the availability of cancer data from many consortia.The purpose of this thesis was to investigate the effects of PIDs on T and B cells and to explore features of neoepitopes in cancers. The object of the first study was to detect the central T cell-specific protein network. The purpose of the second and third studies were to reconstruct the T and B cell network model and simulate the dynamic effects of PID perturbations. The aim of the fourth study was to characterize neoepitopes from pan-cancer datasets.The immunome interactome was reconstructed, and the links weighed with gene expression correlation of integrated, time series data (Paper I). The significance of the weighted links were computed with the Global Statistical Significance (GloSS) method, and the weighted interactome network was filtered to obtain the central T cell network. Next, the T cell network model was reconstructed from literature mining and the core T cell protein interaction network (Paper II). The B cell network model was reconstructed by mining the literature for central B cell interactions (Paper III). The normalized HillCube software was used to study the dynamic effects of PID perturbations in T and B cells. Proteome-wide amino AASs on putatively derived 8-, 9-, 10-, and 11-mer neoepitopes in 30 cancer types were analyzed with the NetMHC 4.0 software (Paper IV).The interconnectedness of the major T cell pathways are maintained in the central T cell PPI network. Empirical evidence from Gene Ontology term and essential genes enrichment analyses were in support for the central T cell network. In the T and B cell simulations for several knockout PIDs correspond to previous results. In the T cell model, simulations for TCR, PTPRC, LCK, ZAP70 and ITK indicated profound disruption in network dynamics. BCL10, CARD11, MALT1, NEMO and MAP3K14 simulations showed significant effects. In B cell, the simulations for LYN, BTK, STIM1, ORAI1, CD19, CD21 and CD81 indicated profound changes to many proteins in the network. Severe effects were observed in the BCL10, IKKB, knockout CARD11, MALT1, NEMO, IKKB and WIPF1 simulations. No major effects were observed for constitutively active PID proteins. The most likely epitopes are those which are detected by several macromolecular histocompartibility complexes (MHCs) and of several peptide lengths. 0.17% of all variants yield more than 100 neoepitopes. Amino acid distributions indicate that variants at all positions in neoepitopes of any length are, on average, more hydrophobic compared to the wild-type.The core T cell network approach is general and applicable to any system with adequate data. The T and B cell models enable the understanding of the dynamic effects of PID disease processes and reveals several novel proteins that may be of interest when diagnosing and treating immunological defects. The neoepitope characteristics can be employed for targeted cancer vaccine applications in personalized therapies

Applying Wikipedia to Interactive Information Retrieval

There are many opportunities to improve the interactivity of information retrieval systems beyond the ubiquitous search box. One idea is to use knowledge bases—e.g. controlled vocabularies, classification schemes, thesauri and ontologies—to organize, describe and navigate the information space. These resources are popular in libraries and specialist collections, but have proven too expensive and narrow to be applied to everyday webscale search. Wikipedia has the potential to bring structured knowledge into more widespread use. This online, collaboratively generated encyclopaedia is one of the largest and most consulted reference works in existence. It is broader, deeper and more agile than the knowledge bases put forward to assist retrieval in the past. Rendering this resource machine-readable is a challenging task that has captured the interest of many researchers. Many see it as a key step required to break the knowledge acquisition bottleneck that crippled previous efforts. This thesis claims that the roadblock can be sidestepped: Wikipedia can be applied effectively to open-domain information retrieval with minimal natural language processing or information extraction. The key is to focus on gathering and applying human-readable rather than machine-readable knowledge. To demonstrate this claim, the thesis tackles three separate problems: extracting knowledge from Wikipedia; connecting it to textual documents; and applying it to the retrieval process. First, we demonstrate that a large thesaurus-like structure can be obtained directly from Wikipedia, and that accurate measures of semantic relatedness can be efficiently mined from it. Second, we show that Wikipedia provides the necessary features and training data for existing data mining techniques to accurately detect and disambiguate topics when they are mentioned in plain text. Third, we provide two systems and user studies that demonstrate the utility of the Wikipedia-derived knowledge base for interactive information retrieval