ShallowHRD status acts as an effective prognostic predictor in ovarian cancer patients treated by poly (ADP-ribose) polymerase inhibitors (PARPis).

PURPOSE: Homologous recombination deficiency (HRD) plays a crucial role in ovarian cancer patients who are treated with Poly (ADP-ribose) polymerase inhibitors (PARPis). It could be defined as a prognosis biomarker. However, many high throughput sequencing methods for evaluating HRD, including HRDetect (WGS 10X), SigMA (WGS 40X or panel 1000X), and scarHRD (WGS 30X), are technically complex, time and data-storage consuming, and costly. Herein, we aimed to develop a low-cost method by low sequencing coverage to identify HRD status for precision medication. METHODS: We utilized ShallowHRD, a software tool to evaluate tumor HRD based on whole genome sequencing (WGS) at low coverage (1X), and established a novel scoring system, ShallowHRD score system. RESULTS: Compared with negative ShallowHRD status (ShallowHRD score < 15 or BRCAwild), positive ShallowHRD status (ShallowHRD score ≥ 15 or BRCAmut) presented favorable survival after being treated with PARPis. CONCLUSION: The ShallowHRD status is a good biomarker for predicting prognosis, which could help guide the clinical application of PARPis in ovarian cancer patients by a cost-effective, time and data-storage saving method.

Kinetoplastid membrane protein-11 adopts a four-helix bundle fold in DPC micelle.

Kinetoplastid membrane protein-11 (KMP11) is a membrane-associated surface protein of kinetoplastids, which has a strong antigenicity but no mammalian homolog, thus representing a promising vaccine candidate. Here, by CD and NMR, we revealed that in buffer, KMP11 assumes a highly helical conformation without stable tertiary packing. Remarkably, upon interacting with dodecylphosphocholine (DPC) micelle, despite minor changes in secondary structures, KMP11 undergoes rearrangements to form a defined structure. We found that its three-dimensional structure unexpectedly adopts the classic four-helix bundle fold. The surface constituted by the N-/C-termini and conserved loop was characterized to dynamically interact with the polar phase of DPC micelle. Our results provide a structural basis for understanding KMP11 functions and further offer a promising avenue for engineering better vaccines. DATABASE: The structure coordinate of KMP11 in DPC micelle has been deposited in PDB with ID of 5Y70 and the associated NMR data were deposited in BMRB with ID of 36112.