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Biology subjects

Tiamiyu, A.

Publications and source records attributed to Tiamiyu, A..

2 recordsLinked to original sources

Full-length next-generation sequencing of 11 HLA loci of more than 1000 individuals from clinical cohorts in East and West Africa

Human Leukocyte Antigen (HLA) loci have been implicated in several diseases from different world populations, including HIV-1. It is necessary to characterize HLA allele variation at the population level prior to investigating associations linked to human diseases. In global databases, limited high-resolution HLA allele types generated by next-generation sequencing (NGS) have been described for populations from African countries. We sought to expand our HLA NGS database to include a total of 1023 participants from multiple HIV clinical studies using full-length HLA genotyping by NGS. Collectively we describe HLA genotypes of individuals from Kenya (n=375), Uganda (n=338), Nigeria (n=139), Tanzania (n=89), and Mozambique (n=82). Overall, we identified 371 unique HLA alleles across 11 loci with the most frequent at each locus being A*02:01:01, B*53:01:01, C*04:01:01, C*06:02:01, DPA1*01:03:01, DPB1*01:01:01, DQA1*01:02:01, DQB1*06:02:01, DRB1*15:03:01, DRB3*02:02:01, DRB4*01:03:01, and DRB5*01:01:01. A total of 25 novel alleles were identified, including 4 with non-synonymous changes affecting the peptide binding groove of HLA molecules. This expansion of NGS based HLA data at the African population level will improve our understanding of human genetic variation and provide insights for vaccine development and targeted personalized therapies.

genetics↗

Deployable CRISPR-Cas13a diagnostic tools to detect and report Ebola and Lassa virus cases in real-time

Viral hemorrhagic fevers (VHFs) remain some of the most devastating human diseases, and recent outbreaks of Ebola virus disease (EVD) 1,2 and Lassa fever (LF) 3,4 highlight the urgent need for sensitive, field-deployable tests to diagnose them 5,6. Here we develop CRISPR-Cas13a-based (SHERLOCK) diagnostics targeting Ebola virus (EBOV) and Lassa virus (LASV), with both fluorescent and lateral flow readouts. We demonstrate on laboratory and clinical samples the sensitivity of these assays and the capacity of the SHERLOCK platform to handle virus-specific diagnostic challenges. Our EBOV diagnostic detects both the L and NP genes, thereby eliminating the potential for false positive results caused by the rVSV{Delta}G-ZEBOV-GP live attenuated vaccine. Our two LASV diagnostics together capture 90% of known viral diversity and demonstrate that CRISPR-RNAs (crRNAs) can be effectively multiplexed to provide greater coverage of known viral diversity. We performed safety testing to demonstrate the efficacy of our HUDSON protocol in heat-inactivating and chemically treating VHF viruses before SHERLOCK testing, eliminating the need for an extraction. We developed a user-friendly field protocol and mobile application (HandLens) to report results, facilitating SHERLOCKs use in endemic regions. Finally, we successfully deployed our tests in Sierra Leone and Nigeria in response to recent outbreaks.

molecular biology↗