centroFlye: Assembling Centromeres with Long Error-Prone Reads

Although variations in centromeres have been linked to cancer and infertility, centromeres still represent the “dark matter of the human genome” and remain an enigma for both biomedical and evolutionary studies. Since centromeres have withstood all previous attempts to develop an automated tool for their assembly and since their assembly using short reads is viewed as intractable, recent efforts attempted to manually assemble centromeres using long error-prone reads. We describe the centroFlye algorithm for centromere assembly using long error-prone reads, apply it for assembling the human X centromere, and use the constructed assembly to gain insights into centromere evolution. Our analysis reveals putative breakpoints in the previous manual reconstruction of the human X centromere and opens a possibility to automatically close the remaining multi-megabase gaps in the reference human genome.