Biology subjects

Liping Liu

Publications and source records attributed to Liping Liu.

3 recordsLinked to original sources

bioRxiv2020

A novel hypoxia gene signature indicates prognosis and reveals the multi-omics molecular landscape of tumour tissue in patients with hepatocellular carcinoma

BackgroundPrevious studies on the impact of hypoxia on hepatocellular carcinoma (HCC) mostly focused on in vitro and animal models. The clinical value of assessing the degree of hypoxia in in vivo tissues and hypoxia-related molecular landscapes in HCC remain poorly defined. MethodsA novel hypoxia gene signature was extracted from hypoxia-treated HCC cells using microarray analysis and a robust rank aggregation algorithm and was verified using public data. Next, the relationships between the hypoxia gene signature and the clinical characteristics and prognoses of HCC patients were analysed. Based on the multi-omics data from The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) and 10 independent HCC cohorts from the Gene Expression Omnibus (GEO), a comprehensive analysis was conducted using the hypoxia gene signature to describe hypoxia-associated multi-omic molecular landscapes and immune microenvironments in HCC tissues. ResultsA 21-gene hypoxia signature was constructed to effectively indicate the exposure of hypoxia in HCC tissues. This novel hypoxia signature and the hypoxia scores calculated based on this signature were closely correlated to some clinical characteristics of HCC patients and can be used to evaluate prognosis. HCC tissues with different hypoxia scores differed significantly in transcriptomic, genomic, epigenomic, and proteomic alterations and immune microenvironments, some of which were related to the clinical prognoses of patients. ConclusionThe 21-gene signature can effectively estimate hypoxia exposure of HCC tissues and has clinical value in the assessment and prediction of the prognosis of HCC patients. Using this 21-gene signature, hypoxia-associated molecular landscapes were described at the tissue level. This comprehensive molecular-level understanding can help to further elucidate the mechanism of hypoxia in tumours and guide clinical cancer therapy. The assessment of the degree of hypoxia is strongly recommended in the personalized treatment of HCC patients to benefit specific patient groups.

cancer biology↗

bioRxiv2015

The Nature, Extent, and Consequences of Genetic Variation in the opa Repeats of Notch in Drosophila

Polyglutamine (pQ) tracts are abundant in many proteins co-interacting on DNA. The lengths of these pQ tracts can modulate their interaction strengths. However, pQ tracts > 40 residues are pathologically prone to amyloidogenic self-assembly. Here, we assess the extent and consequences of variation in the pQ-encoding opa repeats of Notch (N) in Drosophila melanogaster. We use Sanger sequencing to genotype opa sequences (50-CAX repeats), which have resisted assembly using short sequence reads. While the majority of N sequences pertain to reference opa31 (Q13HQ17) and opa32 (Q13HQ18) allelic classes, several rare alleles encode tracts > 32 residues: opa33a (Q14HQ18), opa33b (Q15HQ17), opa34 (Q16HQ17), opa35a1/opa35a2 (Q13HQ21), opa36 (Q13HQ22), and opa37 (Q13HQ23). Only one rare allele encodes a tract < 31 residues: opa23 (Q13-Q10). This opa23 allele shortens the pQ tract while simultaneously eliminating the interrupting histidine. Homozygotes for the short and long opa alleles have defects in sensory bristle organ specification, abdominal patterning, and embryonic survival. Inbred stocks with wild-type opa31 alleles become more viable when outbred, while an inbred stock with the longer opa35 becomes less viable after outcrossing to different backgrounds. In contrast, an inbred stock with the short opa23 allele is semi-viable in both inbred and outbred genetic backgrounds. This opa23 Notch allele also produces notched wings when recombined out of the X chromosome. Importantly, wa-linked X balancers carry the N allele opa33b and suppress AS-C insufficiency caused by the sc8 inversion. Our results demonstrate potent pQ variation and epistatic sensitivity for the N locus, and the need for long read genotyping of key repeat variables underlying gene regulatory networks.

Evolutionary Biology↗

bioRxiv2015

The Nature, Extent, and Consequences of Cryptic Genetic Variation in the opa Repeats of Notch in Drosophila

ABTRACTPolyglutamine (pQ) tracts are abundant in many proteins co-interacting on DNA. The lengths of these pQ tracts can modulate their interaction strengths. However, pQ tracts > 40 residues are pathologically prone to amyloidogenic self-assembly. Here, we assess the extent and consequences of variation in the pQ-encoding opa repeats of Notch (N) in Drosophila melanogaster. We use Sanger sequencing to genotype opa sequences (5-CAX repeats), which have resisted assembly using short sequence reads. While the majority of N sequences pertain to reference opa31 (Q13HQ17) and opa32 (Q13HQ18) allelic classes, several rare alleles encode tracts > 32 residues: opa33a (Q14HQ18), opa33b (Q15HQ17), opa34 (Q16HQ17), opa35a1/opa35a2 (Q13HQ21), opa36 (Q13HQ22), and opa37 (Q13HQ23). Only one rare allele encodes a tract < 31 residues: opa23 (Q13-Q10). This opa23 allele shortens the pQ tract while simultaneously eliminating the interrupting histidine. Homozygotes for the short and long opa alleles have defects in sensory bristle organ specification, abdominal patterning, and embryonic survival. Inbred stocks with wild-type opa31 alleles become more viable when outbred, while an inbred stock with the longer opa35 becomes less viable after outcrossing to different backgrounds. In contrast, an inbred stock with the short opa23 allele is semi-viable in both inbred and outbred genetic backgrounds. This opa23 Notch allele also produces notched wings when recombined out of the X chromosome. Importantly, wa-linked X balancers carry the N allele opa33b and suppress AS-C insufficiency caused by the sc8 inversion. Our results demonstrate significant cryptic variation and epistatic sensitivity for the N locus, and the need for long read genotyping of key repeat variables underlying gene regulatory networks.

Genetics↗