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High-through­put Virus Discov­ery in Next Gener­a­tion Sequenc­ing Data

Franziska Klingler — Hector Fellow Ralf Bartenschlager

Anelloviruses are a diverse group of ubiqui­tous viruses infect­ing humans and verte­brates. Their contri­bu­tion to disease devel­op­ment remains elusive. We hypoth­e­size that during lifelong, persis­tent infec­tion disbal­ances in the viral commu­nity can drive onset and progres­sion of disease, e.g. cancer. We aim at a thorough descrip­tion of the viral spectrum present in healthy and diseased tissue by high-through­put screen­ing of sequenc­ing data and subse­quent identi­fi­ca­tion of viral variants corre­lated with pathogenesis.

Anelloviruses are a highly diverse group of non-enveloped viruses with circu­lar single-stranded DNA genomes ranging between 2.8–3.8 kb. These viruses are ubiqui­tously present in humans and other verte­brates. Often several family members are detected simul­ta­ne­ously within the same tissue where they estab­lish persis­tent infec­tions. Currently, their role in devel­op­ment of human diseases, such as cancer and autoim­mune disor­ders remains elusive. We hypoth­e­size that, although in many cases not causing harm over years, disbal­ances in the compo­si­tion of viral commu­ni­ties can induce disease onset and progression.

We created a power­ful compu­ta­tional platform consist­ing of two modules. The first is termed ‘virushunter’, enabling high-through­put detec­tion of viral sequences in unprocessed Next Gener­a­tion sequenc­ing (NGS) data. The second one, ‘virus­gath­erer’ assem­bles the complete viral genomes. Thus, we are able to identify novel viral species only distantly related to any known viruses in distinct tissues and disease conditions.

Now, we aim at a compre­hen­sive descrip­tion of the spectrum of human anelloviruses by system­at­i­cally screen­ing NGS data of diseased and healthy tissues. We will then perform compu­ta­tional and labora­tory analy­ses to deter­mine i) possi­ble disease associ­a­tion of identi­fied viral species and subgroups, ii) the presence of oncogenes and iii) epidemi­o­log­i­cal data regard­ing the viral preva­lence and the related risk of certain diseases. This will ultimately allow us to thoroughly eluci­date the patho­genic poten­tial of human anelloviruses.

High-throughput Virus Discovery in Next Generation Sequencing Data

Franziska Klingler

Heidel­berg University
   

Super­vised by

Prof. Dr.

Ralf Barten­schlager

Medicine & Biology

Hector Fellow since 2016