DIMA 3.0: Domain Interaction Map

Domain Interaction MAp (DIMA, available at http://webclu.bio.wzw.tum.de/dima) is a database of predicted and known interactions between protein domains. It integrates 5807 structurally known interactions imported from the iPfam and 3did databases and 46 900 domain interactions predicted by four computational methods: domain phylogenetic profiling, domain pair exclusion algorithm correlated mutations and domain interaction prediction in a discriminative way. Additionally predictions are filtered to exclude those domain pairs that are reported as non-interacting by the Negatome database. The DIMA Web site allows to calculate domain interaction networks either for a domain of interest or for entire organisms, and to explore them interactively using the Flash-based Cytoscape Web software

DOMINO: a database of domain–peptide interactions

Many protein interactions are mediated by small protein modules binding to short linear peptides. DOMINO () is an open-access database comprising more than 3900 annotated experiments describing interactions mediated by protein-interaction domains. DOMINO can be searched with a versatile search tool and the interaction networks can be visualized with a convenient graphic display applet that explicitly identifies the domains/sites involved in the interactions

Network analysis of circular permutations in multidomain proteins reveals functional linkages for uncharacterized proteins.

Various studies have implicated different multidomain proteins in cancer. However, there has been little or no detailed study on the role of circular multidomain proteins in the general problem of cancer or on specific cancer types. This work represents an initial attempt at investigating the potential for predicting linkages between known cancer-associated proteins with uncharacterized or hypothetical multidomain proteins, based primarily on circular permutation (CP) relationships. First, we propose an efficient algorithm for rapid identification of both exact and approximate CPs in multidomain proteins. Using the circular relations identified, we construct networks between multidomain proteins, based on which we perform functional annotation of multidomain proteins. We then extend the method to construct subnetworks for selected cancer subtypes, and performed prediction of potential link-ages between uncharacterized multidomain proteins and the selected cancer types. We include practical results showing the performance of the proposed methods

Detecting and comparing non-coding RNAs in the high-throughput era.

In recent years there has been a growing interest in the field of non-coding RNA. This surge is a direct consequence of the discovery of a huge number of new non-coding genes and of the finding that many of these transcripts are involved in key cellular functions. In this context, accurately detecting and comparing RNA sequences has become important. Aligning nucleotide sequences is a key requisite when searching for homologous genes. Accurate alignments reveal evolutionary relationships, conserved regions and more generally any biologically relevant pattern. Comparing RNA molecules is, however, a challenging task. The nucleotide alphabet is simpler and therefore less informative than that of amino-acids. Moreover for many non-coding RNAs, evolution is likely to be mostly constrained at the structural level and not at the sequence level. This results in very poor sequence conservation impeding comparison of these molecules. These difficulties define a context where new methods are urgently needed in order to exploit experimental results to their full potential. This review focuses on the comparative genomics of non-coding RNAs in the context of new sequencing technologies and especially dealing with two extremely important and timely research aspects: the development of new methods to align RNAs and the analysis of high-throughput data

A proteome-wide protein interaction map for Campylobacter jejuni

'Systematic identification of protein interactions for the bacterium Campylobacter jejuni using high-throughput yeast two-hybrid screens detected interactions for 80% of the organism's proteins

Mitmekesiste bioloogiliste andmete ühendamine ja analüüs

Väitekirja elektrooniline versioon ei sisalda publikatsiooneTänu tehnoloogiate arengule on bioloogiliste andmete maht viimastel aastatel mitmekordistunud. Need andmed katavad erinevaid bioloogia valdkondi. Piirdudes vaid ühe andmestikuga saab bioloogilisi protsesse või haigusi uurida vaid ühest aspektist korraga. Seetõttu on tekkinud üha suurem vajadus masinõppe meetodite järele, mis aitavad kombineerida eri valdkondade andmeid, et uurida bioloogilisi protsesse tervikuna. Lisaks on nõudlus usaldusväärsete haigusspetsiifiliste andmestike kogude järele, mis võimaldaks vastavaid analüüse efektiivsemalt läbi viia. Käesolev väitekiri kirjeldab, kuidas rakendada masinõppel põhinevaid integratsiooni meetodeid erinevate bioloogiliste küsimuste uurimiseks. Me näitame kuidas integreeritud andmetel põhinev analüüs võimaldab paremini aru saada bioloogilistes protsessidest kolmes valdkonnas: Alzheimeri tõbi, toksikoloogia ja immunoloogia. Alzheimeri tõbi on vanusega seotud neurodegeneratiivne haigus millel puudub efektiivne ravi. Väitekirjas näitame, kuidas integreerida erinevaid Alzheimeri tõve spetsiifilisi andmestikke, et moodustada heterogeenne graafil põhinev Alzheimeri spetsiifiline andmestik HENA. Seejärel demonstreerime süvaõppe meetodi, graafi konvolutsioonilise tehisnärvivõrgu, rakendamist HENA-le, et leida potentsiaalseid haigusega seotuid geene. Teiseks uurisime kroonilist immuunpõletikulist haigust psoriaasi. Selleks kombineerisime patsientide verest ja nahast pärinevad laboratoorsed mõõtmised kliinilise infoga ning integreerisime vastavad analüüside tulemused tuginedes valdkonnaspetsiifilistel teadmistel. Töö viimane osa keskendub toksilisuse testimise strateegiate edasiarendusele. Toksilisuse testimine on protsess, mille käigus hinnatakse, kas uuritavatel kemikaalidel esineb organismile kahjulikke toimeid. See on vajalik näiteks ravimite ohutuse hindamisel. Töös me tuvastasime sarnase toimemehhanismiga toksiliste ühendite rühmad. Lisaks arendasime klassifikatsiooni mudeli, mis võimaldab hinnata uute ühendite toksilisust.A fast advance in biotechnological innovation and decreasing production costs led to explosion of experimental data being produced in laboratories around the world. Individual experiments allow to understand biological processes, e.g. diseases, from different angles. However, in order to get a systematic view on disease it is necessary to combine these heterogeneous data. The large amounts of diverse data requires building machine learning models that can help, e.g. to identify which genes are related to disease. Additionally, there is a need to compose reliable integrated data sets that researchers could effectively work with. In this thesis we demonstrate how to combine and analyze different types of biological data in the example of three biological domains: Alzheimer’s disease, immunology, and toxicology. More specifically, we combine data sets related to Alzheimer’s disease into a novel heterogeneous network-based data set for Alzheimer’s disease (HENA). We then apply graph convolutional networks, state-of-the-art deep learning methods, to node classification task in HENA to find genes that are potentially associated with the disease. Combining patient’s data related to immune disease helps to uncover its pathological mechanisms and to find better treatments in the future. We analyse laboratory data from patients’ skin and blood samples by combining them with clinical information. Subsequently, we bring together the results of individual analyses using available domain knowledge to form a more systematic view on the disease pathogenesis. Toxicity testing is the process of defining harmful effects of the substances for the living organisms. One of its applications is safety assessment of drugs or other chemicals for a human organism. In this work we identify groups of toxicants that have similar mechanism of actions. Additionally, we develop a classification model that allows to assess toxic actions of unknown compounds.https://www.ester.ee/record=b523255