Fast, accurate and automatic ancient nucleosome and methylation maps with epiPALEOMIX

The first epigenomes from archaic hominins (AH) and ancient anatomically modern humans (AMH) have recently been characterized, based, however, on a limited number of samples. The extent to which ancient genome-wide epigenetic landscapes can be reconstructed thus remains contentious. Here, we present epiPALEOMIX, an open-source and user-friendly pipeline that exploits post-mortem DNA degradation patterns to reconstruct ancient methylomes and nucleosome maps from shotgun and/or capture-enrichment data. Applying epiPALEOMIX to the sequence data underlying 35 ancient genomes including AMH, AH, equids and aurochs, we investigate the temporal, geographical and preservation range of ancient epigenetic signatures. We first assess the quality of inferred ancient epigenetic signatures within well-characterized genomic regions. We find that tissue-specific methylation signatures can be obtained across a wider range of DNA preparation types than previously thought, including when no particular experimental procedures have been used to remove deaminated cytosines prior to sequencing. We identify a large subset of samples for which DNA associated with nucleosomes is protected from post-mortem degradation, and nucleosome positioning patterns can be reconstructed. Finally, we describe parameters and conditions such as DNA damage levels and sequencing depth that limit the preservation of epigenetic signatures in ancient samples. When such conditions are met, we propose that epigenetic profiles of CTCF binding regions can be used to help data authentication. Our work, including epiPALEOMIX, opens for further investigations of ancient epigenomes through time especially aimed at tracking possible epigenetic changes during major evolutionary, environmental, socioeconomic, and cultural shifts

Pamidronate “zebra lines”:A treatment timeline

Osteogenesis imperfecta is a hereditary bone dysplasia characterized by bone fragility, deformity, and short stature. Treatment focuses on preventing bone fractures and symptom relief. Pamidronate, a second-generation bisphosphonate drug that minimizes bone loss, is the chosen treatment in osteogenesis imperfecta. Radiologically, each cycle of pamidronate treatment is depicted as a line of sclerosed nondecalcified cartilage at the metaphysis, termed a pamidronate line. In this case report, we demonstrate that a treatment timeline can be visualized on plain radiographs as the number and spacing of pamidronate lines reflects the number and timing of treatment cycles. The educational value of this is to reassure physicians of the benign nature of “zebra lines,” to demonstrate that the pamidronate lines migrate and fade with bone growth, and alert physicians that the lack of expected pamidronate lines during treatment may reflect a change in the patient's condition that reduces the effectiveness of bisphosphonate infusions