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Annual Scientific Report 2015

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Anton Enright<br />

PhD in Computational Biology, University of<br />

Cambridge, 2003. Postdoctoral research at<br />

Memorial Sloan-Kettering Cancer Center,<br />

New York.<br />

At EMBL-EBI since 2008.<br />

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34709696 34745393 34781090 34816788<br />

Grk4<br />

Htt<br />

Different spliced isoforms detected across multiple murine tissues based<br />

on the CaptureSeq methodology.<br />

MicroRNA evolution and function<br />

The detection of known miRNAs and the prediction<br />

of novel miRNAs are important for our understanding<br />

of the evolution of these molecules and their roles in<br />

functional specialisation. We developed a new algorithm<br />

for the prediction of novel miRNAs from deepsequencing<br />

data and applied this method to the de novo<br />

detection of miRNAs in a number of species. We worked<br />

closely with Elia Benito-Gutierrez from the Arendt<br />

group to define miRNAs in amphioxus species from<br />

around the world and identify miRNAs with distinct<br />

roles in developmental processes.<br />

Computational methods<br />

The epi-transcriptome is a growing area of interest<br />

and post-transcriptional modifications of a number<br />

of different types of RNA are becoming increasingly<br />

important. We developed Chimera, a recently published<br />

tool for the assessment of 3’ Uridylation of miRNAs and<br />

other changes such as adenylation or ADAR editing.<br />

We began to use this system in collaboration with the<br />

O’Carroll laboratory to explore uridylation and RNA<br />

methylation in the murine male germline. Our data<br />

shows the many important epi-transcriptomic changes<br />

present in both microRNAs and mRNAs and how<br />

they respond when key proteins are conditionally<br />

knocked out.<br />

Future plans<br />

In 2016 we will complete our on-going long-term<br />

analysis on lncRNAs in the male germline and D.<br />

melanogaster mesoderm. We will continue to work on<br />

our project to explore the process of genomic integration<br />

of HPV and how this virus can lead to the development<br />

of cervical cancer through sequencing and clinical<br />

genomics. We also plan to release our new tool for the<br />

machine-learning-based prediction of novel microRNAs<br />

from large-scale sequencing data of both finished<br />

genomes and organisms for which a reference genome is<br />

not yet available.<br />

Our long-term goal is to combine regulatory RNA target<br />

prediction, secondary effects and upstream regulation<br />

into complex regulatory networks. We are extremely<br />

interested in the evolution of regulatory RNAs and<br />

developing phylogenetic techniques appropriate for<br />

short, non-coding RNA and long non-coding RNAs. We<br />

will continue to build strong links with experimental<br />

laboratories that work on miRNAs in different systems,<br />

as this will allow us to build better datasets with which<br />

to train and validate our computational approaches.<br />

The use of visualisation techniques to assist with<br />

the interpretation and display of complex, multidimensional<br />

data will continue to be an important<br />

parallel aspect of our work.<br />

<strong>2015</strong> EMBL-EBI <strong>Annual</strong> <strong>Scientific</strong> <strong>Report</strong> 136

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