Genome-Wide Detection for Runs of Homozygosity in Baoshan Pigs Using Whole Genome Resequencing.

Baoshan pigs (BS) are a local breed in Yunnan Province that may face inbreeding owing to its limited population size. To accurately evaluate the inbreeding level of the BS pig population, we used whole-genome resequencing to identify runs of homozygosity (ROH) regions in BS pigs, calculated the inbreeding coefficient based on pedigree and ROH, and screened candidate genes with important economic traits from ROH islands. A total of 22,633,391 SNPS were obtained from the whole genome of BS pigs, and 201 ROHs were detected from 532,450 SNPS after quality control. The number of medium-length ROH (1-5 Mb) was the highest (98.43%), the number of long ROH (>5 Mb) was the lowest (1.57%), and the inbreeding of BS pigs mainly occurred in distant generations. The inbreeding coefficient FROH, calculated based on ROH, was 0.018 ± 0.016, and the FPED, calculated based on the pedigree, was 0.027 ± 0.028, which were positively correlated. Forty ROH islands were identified, containing 507 genes and 891 QTLs. Several genes were associated with growth and development (IGFALS, PTN, DLX5, DKK1, WNT2), meat quality traits (MC3R, ACSM3, ECI1, CD36, ROCK1, CACNA2D1), and reproductive traits (NPW, TSHR, BMP7). This study provides a reference for the protection and utilization of BS pigs.

Identification of cell surface markers for acute myeloid leukemia prognosis based on multi-model analysis.

Given the extremely high inter-patient heterogeneity of acute myeloid leukemia (AML), the identification of biomarkers for prognostic assessment and therapeutic guidance is critical. Cell surface markers (CSMs) have been shown to play an important role in AML leukemogenesis and progression. In the current study, we evaluated the prognostic potential of all human CSMs in 130 AML patients from The Cancer Genome Atlas (TCGA) based on differential gene expression analysis and univariable Cox proportional hazards regression analysis. By using multi-model analysis, including Adaptive LASSO regression, LASSO regression, and Elastic Net, we constructed a 9-CSMs prognostic model for risk stratification of the AML patients. The predictive value of the 9-CSMs risk score was further validated at the transcriptome and proteome levels. Multivariable Cox regression analysis showed that the risk score was an independent prognostic factor for the AML patients. The AML patients with high 9-CSMs risk scores had a shorter overall and event-free survival time than those with low scores. Notably, single-cell RNA-sequencing analysis indicated that patients with high 9-CSMs risk scores exhibited chemotherapy resistance. Furthermore, PI3K inhibitors were identified as potential treatments for these high-risk patients. In conclusion, we constructed a 9-CSMs prognostic model that served as an independent prognostic factor for the survival of AML patients and held the potential for guiding drug therapy.

Multi-omics and pharmacological characterization of patient-derived glioma cell lines.

Glioblastoma (GBM) is the most common brain tumor and remains incurable. Primary GBM cultures are widely used tools for drug screening, but there is a lack of genomic and pharmacological characterization for these primary GBM cultures. Here, we collect 50 patient-derived glioma cell (PDGC) lines and characterize them by whole genome sequencing, RNA sequencing, and drug response screening. We identify three molecular subtypes among PDGCs: mesenchymal (MES), proneural (PN), and oxidative phosphorylation (OXPHOS). Drug response profiling reveals that PN subtype PDGCs are sensitive to tyrosine kinase inhibitors, whereas OXPHOS subtype PDGCs are sensitive to histone deacetylase inhibitors, oxidative phosphorylation inhibitors, and HMG-CoA reductase inhibitors. PN and OXPHOS subtype PDGCs stably form tumors in vivo upon intracranial transplantation into immunodeficient mice, whereas most MES subtype PDGCs fail to form tumors in vivo. In addition, PDGCs cultured by serum-free medium, especially long-passage PDGCs, carry MYC/MYCN amplification, which is rare in GBM patients. Our study provides a valuable resource for understanding primary glioma cell cultures and clinical translation and highlights the problems of serum-free PDGC culture systems that cannot be ignored.