scholarly journals HLA allele-specific expression loss in tumors can shorten survival and hinder immunotherapy

2020 ◽  
Author(s):  
Ioan Filip ◽  
Rose Orenbuch ◽  
Junfei Zhao ◽  
Gulam Manji ◽  
Evangelina López de Maturana ◽  
...  
Keyword(s):  
Overall Survival ◽  
Human Leukocyte ◽  
Prognostic Indicator ◽  
Cancer Prognosis ◽  
Sequencing Data ◽  
Specific Expression ◽  
Allele Specific Expression ◽  
Allele Specific ◽  
Tumor Types ◽  
Expression Loss

AbstractEfficient presentation of aberrant peptide fragments by the human leukocyte antigen class I (HLA-I) genes is necessary for immune detection and killing of cancer cells. Patient HLA-I genotypes are known to impact the efficacy of cancer immunotherapy, and the somatic loss of HLA-I heterozygosity has been established as a factor in immune evasion. While global deregulated expression of HLA-I has been reported in different tumor types, the role of HLA-I allele-specific expression loss – that is, the preferential RNA expression loss of specific HLA-I alleles – has not been fully characterized in cancer. In the present study, we quantified HLA-I allele-specific expression (ASE) across eleven TCGA tumor types using a novel method from input RNA and whole-exome sequencing data. Allele-specific loss in at least one of the three HLA-I genes (ASE loss) was pervasive and associated to worse overall survival across tumor types, including pancreatic adenocarcinomas, prostate carcinomas and glioblastomas, among others. In particular, our analysis shows that detection of neoantigens with binding affinity to the specific HLA-I genes subject to ASE loss was a top prognostic indicator of overall survival. Additionally, we found that ASE loss hindered immunotherapy in retrospective analyses. Together, these results highlight the prevalence of HLA-I ASE loss – a previously uncharacterized phenomenon in cancer – and provide initial evidence of its clinical significance in cancer prognosis and immunotherapy treatment.

scholarly journals Patterns of genome-wide allele-specific expression in hybrid rice and the implications on the genetic basis of heterosis

2019 ◽  
Vol 116 (12) ◽  
pp. 5653-5658 ◽  
Author(s):  
Lin Shao ◽  
Feng Xing ◽  
Conghao Xu ◽  
Qinghua Zhang ◽  
Jian Che ◽  
...  
Keyword(s):  
Genetic Basis ◽  
Molecular Mechanisms ◽  
Sequencing Data ◽  
Specific Expression ◽  
Allele Specific Expression ◽  
Parental Allele ◽  
Genetic Components ◽  
Genome Wide ◽  
A Genome ◽  
Allele Specific

Utilization of heterosis has greatly increased the productivity of many crops worldwide. Although tremendous progress has been made in characterizing the genetic basis of heterosis using genomic technologies, molecular mechanisms underlying the genetic components are much less understood. Allele-specific expression (ASE), or imbalance between the expression levels of two parental alleles in the hybrid, has been suggested as a mechanism of heterosis. Here, we performed a genome-wide analysis of ASE by comparing the read ratios of the parental alleles in RNA-sequencing data of an elite rice hybrid and its parents using three tissues from plants grown under four conditions. The analysis identified a total of 3,270 genes showing ASE (ASEGs) in various ways, which can be classified into two patterns: consistent ASEGs such that the ASE was biased toward one parental allele in all tissues/conditions, and inconsistent ASEGs such that ASE was found in some but not all tissues/conditions, including direction-shifting ASEGs in which the ASE was biased toward one parental allele in some tissues/conditions while toward the other parental allele in other tissues/conditions. The results suggested that these patterns may have distinct implications in the genetic basis of heterosis: The consistent ASEGs may cause partial to full dominance effects on the traits that they regulate, and direction-shifting ASEGs may cause overdominance. We also showed that ASEGs were significantly enriched in genomic regions that were differentially selected during rice breeding. These ASEGs provide an index of the genes for future pursuit of the genetic and molecular mechanism of heterosis.

scholarly journals Effect of read-mapping biases on detecting allele-specific expression from RNA-sequencing data

2009 ◽  
Vol 25 (24) ◽  
pp. 3207-3212 ◽  
Author(s):  
Jacob F. Degner ◽  
John C. Marioni ◽  
Athma A. Pai ◽  
Joseph K. Pickrell ◽  
Everlyne Nkadori ◽  
...  
Keyword(s):  
Rna Sequencing ◽  
Sequencing Data ◽  
Read Mapping ◽  
Specific Expression ◽  
Allele Specific Expression ◽  
Allele Specific

scholarly journals Genome and Transcriptome Sequencing of Populus × sibirica Identified Sex-Associated Allele-Specific Expression of the CLC Gene

2021 ◽  
Vol 12 ◽  
Author(s):  
Elena N. Pushkova ◽  
George S. Krasnov ◽  
Valentina A. Lakunina ◽  
Roman O. Novakovskiy ◽  
Liubov V. Povkhova ◽  
...  
Keyword(s):  
Transcriptome Sequencing ◽  
Dna Methyltransferase ◽  
Sequencing Data ◽  
Specific Expression ◽  
Allelic Variants ◽  
Allele Specific Expression ◽  
T Complex ◽  
Populus Suaveolens ◽  
Complex Protein ◽  
Allele Specific

Transcriptome sequencing of leaves, catkin axes, and flowers from male and female trees of Populus × sibirica and genome sequencing of the same plants were performed for the first time. The availability of both genome and transcriptome sequencing data enabled the identification of allele-specific expression. Such an analysis was performed for genes from the sex-determining region (SDR). P. × sibirica is an intersectional hybrid between species from sections Aigeiros (Populus nigra) and Tacamahaca (Populus laurifolia, Populus suaveolens, or Populus × moskoviensis); therefore, a significant number of heterozygous polymorphisms were identified in the SDR that allowed us to distinguish between alleles. In the SDR, both allelic variants of the TCP (T-complex protein 1 subunit gamma), CLC (Chloride channel protein CLC-c), and MET1 (DNA-methyltransferase 1) genes were expressed in females, while in males, two allelic variants were expressed for TCP and MET1 but only one allelic variant prevailed for CLC. Targeted sequencing of TCP, CLC, and MET1 regions on a representative set of trees confirmed the sex-associated allele-specific expression of the CLC gene in generative and vegetative tissues of P. × sibirica. Our study brings new knowledge on sex-associated differences in Populus species.

scholarly journals Genome-wide analysis of allele-specific expression of genes in the model diatom Phaeodactylum tricornutum

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Antoine Hoguin ◽  
Achal Rastogi ◽  
Chris Bowler ◽  
Leila Tirichine
Keyword(s):  
Phaeodactylum Tricornutum ◽  
Protein Transport ◽  
Natural Hybridization ◽  
Allelic Expression ◽  
Monoallelic Expression ◽  
Sequencing Data ◽  
Specific Expression ◽  
Allele Specific Expression ◽  
Biallelic Expression ◽  
Allele Specific

AbstractRecent advances in next generation sequencing technologies have allowed the discovery of widespread autosomal allele-specific expression (aASE) in mammals and plants with potential phenotypic effects. Extensive numbers of genes with allele-specific expression have been described in the diatom Fragilariopsis cylindrus in association with adaptation to external cues, as well as in Fistulifera solaris in the context of natural hybridization. However, the role of aASE and its extent in diatoms remain elusive. In this study, we investigate allele-specific expression in the model diatom Phaeodactylum tricornutum by the re-analysis of previously published whole genome RNA sequencing data and polymorphism calling. We found that 22% of P. tricornutum genes show moderate bias in allelic expression while 1% show nearly complete monoallelic expression. Biallelic expression associates with genes encoding components of protein metabolism while moderately biased genes associate with functions in catabolism and protein transport. We validated candidate genes by pyrosequencing and found that moderate biases in allelic expression were less stable than monoallelically expressed genes that showed consistent bias upon experimental validations at the population level and in subcloning experiments. Our approach provides the basis for the analysis of aASE in P. tricornutum and could be routinely implemented to test for variations in allele expression under different environmental conditions.

scholarly journals cisASE: a likelihood-based method for detecting putativecis-regulated allele-specific expression in RNA sequencing data

2016 ◽  
Vol 32 (21) ◽  
pp. 3291-3297 ◽  
Author(s):  
Zhi Liu ◽  
Tuantuan Gui ◽  
Zhen Wang ◽  
Hong Li ◽  
Yunhe Fu ◽  
...  
Keyword(s):  
Rna Sequencing ◽  
Sequencing Data ◽  
Specific Expression ◽  
Allele Specific Expression ◽  
Allele Specific

scholarly journals Investigation of allele specific expression in various tissues of broiler chickens using the detection tool VADT

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
M. Joseph Tomlinson ◽  
Shawn W. Polson ◽  
Jing Qiu ◽  
Juniper A. Lake ◽  
William Lee ◽  
...  
Keyword(s):  
Broiler Chickens ◽  
Nucleotide Polymorphisms ◽  
Rna Seq ◽  
Specific Expression ◽  
Single Nucleotide ◽  
Allele Specific Expression ◽  
Detection Tool ◽  
Commercial Broiler ◽  
Significant Phenomenon ◽  
Allele Specific

AbstractDifferential abundance of allelic transcripts in a diploid organism, commonly referred to as allele specific expression (ASE), is a biologically significant phenomenon and can be examined using single nucleotide polymorphisms (SNPs) from RNA-seq. Quantifying ASE aids in our ability to identify and understand cis-regulatory mechanisms that influence gene expression, and thereby assist in identifying causal mutations. This study examines ASE in breast muscle, abdominal fat, and liver of commercial broiler chickens using variants called from a large sub-set of the samples (n = 68). ASE analysis was performed using a custom software called VCF ASE Detection Tool (VADT), which detects ASE of biallelic SNPs using a binomial test. On average ~ 174,000 SNPs in each tissue passed our filtering criteria and were considered informative, of which ~ 24,000 (~ 14%) showed ASE. Of all ASE SNPs, only 3.7% exhibited ASE in all three tissues, with ~ 83% showing ASE specific to a single tissue. When ASE genes (genes containing ASE SNPs) were compared between tissues, the overlap among all three tissues increased to 20.1%. Our results indicate that ASE genes show tissue-specific enrichment patterns, but all three tissues showed enrichment for pathways involved in translation.

scholarly journals Analysis of Allele-Specific Expression in Mouse Liver by RNA-Seq: A Comparison With Cis-eQTL Identified Using Genetic Linkage

Genetics ◽  
2013 ◽  
Vol 195 (3) ◽  
pp. 1157-1166 ◽  
Author(s):  
Sandrine Lagarrigue ◽  
Lisa Martin ◽  
Farhad Hormozdiari ◽  
Pierre-François Roux ◽  
Calvin Pan ◽  
...  
Keyword(s):  
Mouse Liver ◽  
Genetic Linkage ◽  
Rna Seq ◽  
Specific Expression ◽  
Allele Specific Expression ◽  
Allele Specific
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