DIPAN: Detecting personalized intronic polyadenylation derived neoantigens from RNA sequencing data.

Intronic polyadenylation (IPA) refers to a particular type of alternative polyadenylation where a gene makes use of a polyadenylation site located within its introns. Aberrant IPA events have been observed in various types of cancer. IPA can produce noncoding transcripts or truncated protein-coding transcripts with altered coding sequences in the resulting protein product. Therefore, IPA events hold the potential to act as a reservoir of tumor neoantigens. Here, we developed a computational method termed DIPAN, which incorporates IPA detection, protein fragmentation, and MHC binding prediction to predict IPA-derived neoantigens. Utilizing RNA-seq from breast cancer cell lines and ovarian cancer clinical samples, we demonstrated the significant contribution of IPA events to the neoantigen repertoire. Through mass spectrometry immunopeptidome analysis, we further illustrated the processing and presentation of IPA-derived neoantigens on the surface of cancer cells. While most IPA-derived neoantigens are sample-specific, shared neoantigens were identified in both cancer cell lines and clinical samples. Furthermore, we demonstrated an association between IPA-derived neoantigen burden and overall survival in cancer patients.

Comprehensive characterization of somatic mutations associated with chimeric RNAs in human cancers.

Chimeric RNAs, which can arise from gene recombination at the DNA level or non-canonical splicing events at the RNA level, have been identified as important roles in human tumors. Dysregulated gene expression caused by somatic mutations and altered splicing patterns of oncogenes or tumor suppressor genes can contribute to the development of tumors. Therefore, investigating the formation mechanism of chimeric RNAs via somatic mutations is critical for understanding tumor pathogenesis. This project is the first to propose studying the association between somatic single nucleotide variants and chimeric RNAs, identifying around 2900 somatic SNVs affecting chimeric RNAs in pan-cancer level. The somatic SNVs on chimeric RNAs were commonly observed in various types of tumor tissues, providing a valuable resource for future study. Additionally, these SNVs show distinct tumor specificity, and those with high frequency had a significant impact on the survival time of patients with tumors. Further research revealed that somatic SNVs associated with chimeric RNA (chiR-SNVs) were typically found within 10 nt of the junction site of chimeric RNAs and had a particularly significant effect on chimeric RNAs from different chromosomes. The enrichment analysis revealed that chiR-SNVs were significantly overrepresented in oncogenes and genes related to RNA binding proteins involved in RNA splicing, which could imply that chiR-SNVs may disrupt the process of RNA splicing and induce the occurrence of chimeric RNAs. This study sheds light on the potential molecular interaction mechanism between somatic SNVs and chimeric RNAs, which opens up a new avenue for researching disease pathway and tumorigenesis development.

Association between SUMF1 polymorphisms and COVID-19 severity.

BACKGROUND: Evidence shows that genetic factors play important roles in the severity of coronavirus disease 2019 (COVID-19). Sulfatase modifying factor 1 (SUMF1) gene is involved in alveolar damage and systemic inflammatory response. Therefore, we speculate that it may play a key role in COVID-19. RESULTS: We found that rs794185 was significantly associated with COVID-19 severity in Chinese population, under the additive model after adjusting for gender and age (for C allele = 0.62, 95% CI = 0.44-0.88, P = 0.0073, logistic regression). And this association was consistent with this in European population Genetics Of Mortality In Critical Care (GenOMICC: OR for C allele = 0.94, 95% CI = 0.90-0.98, P = 0.0037). Additionally, we also revealed a remarkable association between rs794185 and the prothrombin activity (PTA) in subjects (P = 0.015, Generalized Linear Model). CONCLUSIONS: In conclusion, our study for the first time identified that rs794185 in SUMF1 gene was associated with the severity of COVID-19.

Litter input decreased the response of soil organic matter decomposition to warming in two subtropical forest soils.

Interaction effect of temperature and litter input on SOM decomposition is poor understood, restricting accurate prediction of the dynamics and stocks of soil organic carbon under global warming. To address this knowledge gap, we conducted an incubation experiment by adding (13)C labeled leaf-litter into a coniferous forest (CF) soil and a broadleaved forest (BF) soil. In this experiment, response of the temperature sensitivity (Q10) of SOM decomposition to the increase in litter input was investigated. The temperature dependences of priming effect (PE) and soil microbial community were analyzed. The Q10 for CF soil significantly decreased from 2.41 in no-litter treatment to 2.05 in litter-added treatment and for BF soil from 2.14 to 1.82, suggesting that litter addition decreases the Q10. PE in the CF soil was 24.9% at 20 °C and 6.2% at 30 °C, and in the BF soil the PE was 8.8% at 20 °C and -7.0% at 30 °C, suggesting that PE decreases with increasing temperature. Relative PE was positively related to the concentrations of Gram-negative bacterial and fungal PLFAs. This study moves a step forward in understanding warming effect on forest carbon cycling by highlighting interaction effect of litter input and warming on soil carbon cycling.

Nitrogen Addition Altered the Effect of Belowground C Allocation on Soil Respiration in a Subtropical Forest.

The availabilities of carbon (C) and nitrogen (N) in soil play an important role in soil carbon dioxide (CO2) emission. However, the variation in the soil respiration (Rs) and response of microbial community to the combined changes in belowground C and N inputs in forest ecosystems are not yet fully understood. Stem girdling and N addition were performed in this study to evaluate the effects of C supply and N availability on Rs and soil microbial community in a subtropical forest. The trees were girdled on 1 July 2012. Rs was monitored from July 2012 to November 2013, and soil microbial community composition was also examined by phospholipid fatty acids (PLFAs) 1 year after girdling. Results showed that Rs decreased by 40.5% with girdling alone, but N addition only did not change Rs. Interestingly, Rs decreased by 62.7% under the girdling with N addition treatment. The reducing effect of girdling and N addition on Rs differed between dormant and growing seasons. Girdling alone reduced Rs by 33.9% in the dormant season and 54.8% in the growing season compared with the control. By contrast, girdling with N addition decreased Rs by 59.5% in the dormant season and 65.4% in the growing season. Girdling and N addition significantly decreased the total and bacterial PLFAs. Moreover, the effect of N addition was greater than girdling. Both girdling and N addition treatments separated the microbial groups on the basis of the first principal component through principal component analysis compared with control. This indicated that girdling and N addition changed the soil microbial community composition. However, the effect of girdling with N addition treatment separated the microbial groups on the basis of the second principal component compared to N addition treatment, which suggested N addition altered the effect of girdling on soil microbial community composition. These results suggest that the increase in soil N availability by N deposition alters the effect of belowground C allocation on the decomposition of soil organic matter by altering the composition of the soil microbial community.