Konak-patojen protein etkileşiminin hesaplamalı yöntemler ile tahmini

06.03.2018 tarihli ve 30352 sayılı Resmi Gazetede yayımlanan “Yükseköğretim Kanunu İle Bazı Kanun Ve Kanun Hükmünde Kararnamelerde Değişiklik Yapılması Hakkında Kanun” ile 18.06.2018 tarihli “Lisansüstü Tezlerin Elektronik Ortamda Toplanması, Düzenlenmesi ve Erişime Açılmasına İlişkin Yönerge” gereğince tam metin erişime açılmıştır.Türler arası patojen-konak protein etkileşimlerin bilinmesi enfeksiyonel hastalıkların teşhis ve tedavisi için geliştirilecek çözüm stratejileri açısından hayati öneme sahiptir. Etkileşim tespitinde kullanılan deneysel yöntemlerin maliyetli olması ve uzun zaman almasından dolayı proteinler arası etkileşimlerin modellendiği hesaplamalı yöntemlerin bu alanda önemli bir yeri vardır. Hesaplamalı yöntemler, tespit süresinin kısaltılması ve maliyetin düşürülmesine ek olarak deneysel yöntemlerle yanlış tespit edilen etkileşimlerin kontrolünde de kullanılmaktadır. Veri seyrekliği, veri yetersizliği ve doğrulanmış negatif veri setinin olmaması, patojen-konak protein etkileşim tahmini için kullanılan hesaplamalı yöntemlerin ortak problemidir. Bu çalışmada amaç patojen-konak etkileşim tahmin doğruluğunu arttırmak ve veri yetersizliğinden kaynaklanan olumsuzlukları gidermektir. Bu kapsamda genişletilmiş ağ modeli ve lokasyon tabanlı kodlama yöntemleri önerildi. Genişletilmiş ağ modeli türler arası yeterli etkileşim verisinin olmadığı patojen konak etkileşimleri ile patojen ve konak proteinlere ait tür içi etkileşimlerin entegre edilmesi tahmin doğruluğunu arttırır hipotezinden esinlenerek geliştirildi. Lokasyon tabanlı kodlama, proteinlerin amino asit diziliminin kodlandığı bir öznitelik çıkarım yöntemidir. Makine öğrenmesi algoritmalarında patojen konak etkileşim tahmininde başarımı etkileyen faktörlerden biri kullanılan özniteliklerdir. Biyolojik veri tabanlarında proteinlere ait en fazla veri amino asit dizilim bilgisidir. Sadece amino asit dizilimini baz alarak geliştirilen güçlü bir öznitelik çıkarım yöntemi, patojen konak etkileşim tahmin doğruluğunu arttıracaktır. Ayrıca amino asit dizilim bilgisinin kullanılması sayesinde bilinen tüm etkileşimler için öznitelik vektörlerinin daha kolay çıkarılması sağlanır. Tezde protein kodlama ve protein etkileşim tahmini üzerine çalışan araştırmacıların kullanılabileceği, ücretsiz erişilebilen, kullanıcı dostu bir ara yüze sahip web tabanlı PROSES (Protein Sequencebased encoding system) yazılımı geliştirildi. Yazılım özellikle programlama bilgisi olmayan kişiler için faydalıdır. PROSES şu anda Yalova Üniversitesi web sunucusunda yer alan http://proses.yalova.edu.tr adresinde kullanılmaktadır.Knowledge of the pathogen-host protein interactions in the inter species has a vital prospect for a solution strategy to be developed against diagnosis and treatment of infectious diseases. Modeling interactions between proteins has necessitated the development of computational methods in this field, since detection of interactions by experimental methods is both time-consuming and costly. Computational methods are used in decreasing of the detection time and cost; in addition checking of the false detected interactions via experimental methods. Data scarcity, data inadequacy, and negative data sampling are the common problems of computational methods for used in prediction of pathogen-host protein interaction. In this study, the purpose is that prediction accuracy of the pathogen-host interaction increase and negativeness eliminate because of data inadequacy. Within thisframework, extended network model and location based encoding approaches are proposed. Firstly, the extended network model is created by inspired from the hypothesis of that integrating the known protein interactions within host and pathogen organisms improve the success of prediction of unknown pathogen-host interactions. Secondly, location based encoding is feature extraction method which is used for encoding of amino acid sequences. One of the important factors is feature which affects success in prediction of pathogen-host interaction within machine learning algorithms. In biological databases, the most data is the information of amino acid sequence regarding proteins. Prediction accuracy of pathogen-host interaction will be increased by that a robust feature extraction method is developed on the basis amino acidsequence. Furthermore, extraction of feature vectors for all the known interactions are provided in easier way by the sake of using the information of amino acid sequence. In this thesis, PROSES (Protein SequencebasedEncodingSystem) which is a user-friendly interface and freely accessible web server, has been designed for researchers, who are working on the field of protein encoding and prediction of protein interaction. The web server is especially useful for those who are not familiar with programming languages. PROSES is currently being used at http://proses.yalova.edu.tr which is storedin the web server of Yalova University

Multitask matrix completion for learning protein interactions across diseases

Disease causing pathogens such as viruses, introduce their proteins into the host cells where they interact with the host’s proteins enabling the virus to replicate inside the host. These interactions between pathogen and host proteins are key to understanding infectious diseases. Often multiple diseases involve phylogenetically related or biologically similar pathogens. Here we present a multitask learning method to jointly model interactions between human proteins and three different, but related viruses: Hepatitis C, Ebola virus and Influenza A. Our multitask matrix completion based model uses a shared low-rank structure in addition to a task-specific sparse structure to incorporate the various interactions. We obtain upto a 39% improvement in predictive performance over prior state-of-the-art models. We show how our model’s parameters can be interpreted to reveal both general and specific interactionrelevant characteristics of the viruses. Our code and data is available at: http://www.cs.cmu.edu/~mkshirsa/bsl_mtl.tg

Weighted Semi-Supervised Approaches for Predictive Modeling and Truth Discovery

Multi-View Learning (MVL) is a framework which combines data from heteroge- neous sources in an efficient manner in which the different views learn from each other, thereby improving the overall prediction of the task. By not combining the data from different views together, we preserve the underlying statistical property of each view thereby learning from data in their original feature space. Additionally, MVL also mitigates the problem of high dimensionality when data from multiple sources are integrated. We have exploited this property of MVL to predict chemical-target and drug-disease associations. Every chemical or drug can be represented in diverse feature spaces that could be viewed as multiple views. Similarly multi-task learning (MTL) frameworks enables the joint learning of related tasks that improves the overall performances of the tasks than learning them individually. This factor allows us to learn related targets and related diseases together. An empirical study has been carried out to study the combined effects of multi-view multi-task learning (MVMTL) to pre- dict chemical-target interactions and drug-disease associations. The first half of the thesis focuses on two methods that closely resemble MVMTL. We first explain the weighted Multi-View learning (wMVL) framework that systemat- ically learns from heterogeneous data sources by weighting the views in terms of their predictive power. We extend the work to include multi-task learning and formulate the second method called Multi-Task with weighted Multi-View Learning (MTwMVL). The performance of these two methods have been evaluated by cheminformatics data sets. iiWe change gears for the second part of this thesis towards truth discovery (TD). Truth discovery closely resembles a multi-view setting but the two strongly differ in certain aspects. While the underlying assumption in multi-view learning is that the different views have label consistency, truth finding differs in its setup where the main objective is to find the true value of an object given that different sources might conflict with each other and claim different values for that object. The sources could be considered as views and the primary strategy in truth finding is to estimate the reliability of each source and its contribution to the truth. There are many methods that address various challenges and aspects of truth discovery and we have in this thesis looked at TD in a semi-supervised setting. As the third contribution to this dissertation, we adopt a semi-supervised truth dis- covery framework in which we consider the labeled objects and unlabeled objects as two closely related tasks with one task having strong labels while the other task hav- ing weak labels. We show that a small set of ground truth helps in achieving better accuracy than the unsupervised methods