 The article discusses the challenges of sequencing genomes or genomic regions with extremely biased base composition using current next generation sequencing, NGS, platforms. The authors have developed an optimized library preparation procedures suitable for low-quantity starting material and tolerant to extremely high AT content sequences. They used these optimized conditions in parallel with standard methods to prepare Illumina sequencing libraries from a non-clinical and a clinical isolate containing 53% host contamination. The results showed that the optimized conditions involving a PCR additive, TMAC, produced amplified libraries with improved coverage of extremely AT-rich regions and reduced bias toward GC neutral templates. This development will greatly benefit sequencing clinical samples that often require amplification due to low mass of DNA starting material. This article was authored by Oyola Samuel O, Otto Thomas D, Jiyu Yong, and others. We are article.tv, links in the description below.