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The novel virus genotyping tool (STAR) and its use in subtyping Human Immunodeficiency Virus Type-1 and Hepatitis B viruses. Richard Myers1, Catherine V. Gale1, Caroline Clark1, Julie Bennett1, Richard S. Tedder1, Ian G. Williams2 and Paul Kellam1 Department of Infection1 and Department of Sexually Transmitted Diseases2, University College London. We have developed a high throughput computational tool for assigning a genotype (subtype) to medically important human viruses Human Immunodeficiency virus type 1 (HIV-1) and Hepatitis B virus (HBV). The HIV subtyping tool works on protease and reverse transcriptase (PR-RT) amino acid sequence, generated routinely for detecting genotypic drug resistance whereas the HBV tool works on the whole virus genome. Subtype specific profiles were created by generation of position specific scoring matrices (PSSMs) from multiple amino acids or nucleotide alignments of HIV-1 and HBV sequence data from GenBank, divided into subtypes A, AG, B, C, D, F, G, H, J and K, and the separate groups N and O for HIV and subtypes A-H for HBV. Sequences of unknown subtype are aligned with these profiles and a discrete odds ratio score is derived from variant amino acid (or nucleotide) positions in the unknown sequence, compared to the normalized frequency distribution of amino acids (or nucleotides) at the corresponding position in the subtype alignment. The highest score is used to assign subtype to the query sequence. Leave one out cross validation analysis showed Subtype Analyser (STAR) was 98%(HIV-1) to 100%(HBV) accurate in subtype assignation and performed as well, or better, compared to other publicly available subtyping methods. STAR was used to classify HIV-1 PR-RT sequences from 843 HIV-1 clinical isolates submitted for drug resistance profiling in London, 885 HIV-1 sequences from Birmingham and from 71 sequences obtained from the Caribbean. Within the London and Birmingham cohorts 28% and 21% of sequences respectively were classified by STAR as non-B subtypes, whereas within the Caribbean dataset, 10% were classified as non-B. The accuracy and validated scoring mechanism of STAR will allow the investigation of the impact of virus subtypes on clinical outcomes of infection.