Project description:In order to more accurately discover the cause of drug resistance in tumor treatment, and to provide a new basis for precise treatment.
Therefore, based on the umbrella theory of precision medicine, we carried out this single-center, prospective, and observational study to include patients with liver metastases from colorectal cancer. By combining genome, transcriptome, and proteomic sequencing data, we established a basis for colorectal cancer liver Transfer the multi-omics data of the sample, describe the reason for the resistance of the first-line treatment, and search for new therapeutic targets.
Project description:Despite being essential for fertility, genome defence pathway genes often evolve rapidly. However, little is known about the molecular basis of this adaptation. Here, we characterize the evolution of a protein interaction network within the PIWI-interacting small RNA (piRNA) genome defence pathway in Drosophila at unprecedented scale and evolutionary resolution. We uncover pervasive rapid evolution of a protein interaction network anchored at the Heterochromatin Protein 1 (HP1) paralog Rhino. Using complementary phylogenetic analysis, high-throughput yeast-two-hybrid matrix screening, and in vivo interaction analyses in cross-species transgenic flies, we characterized at least three distinct evolutionary protein interaction trajectories across ~40 million years of Drosophila evolution. The comprehensive cross-species interaction data set covering 11 piRNA pathway proteins of five Drosophila species revealed several protein interactions that are fully conserved, indicating functional conservation despite overall rapid amino acid sequence change. Other interactions are preserved through co-evolution and were detected only between proteins in closely related and within species. We also identified sets of species-restricted protein interactions which, through rewiring of a Rhino-anchored transcription factor network, may preserve critical roles in enabling and adapting piRNA production from heterochromatic loci. In sum, our analyses dissected principles of interaction evolution in an adaptively evolving protein-protein interaction network uncovering evolutionary and functional insight into germline piRNA production across Drosophila species. Our work provides key experimental evidence in support of a fundamental model proposing that intermolecular interaction innovation is a major molecular mechanism of evolutionary adaptation in protein-coding genes.
Project description:Species often produce sterile hybrids early in their evolutionary divergence, and some evidence suggests that hybrid sterility may be associated with deviations or disruptions in gene expression. In support of this idea, many studies have shown that a high proportion of male-biased genes are underexpressed compared to non-sex-biased genes in sterile F1 male hybrids of Drosophila species. In this study, we examined and compared patterns of misexpression in 4 day old sterile male F1 hybrids of Drosophila simulans and its sibling species, D. mauritiana. We analyzed hybrids using genome-wide D. melanogaster arrays from the Drosophila Genome Resource Center (DGRC). The results from a custom array (GPL4022) for this species pair, from the custom array and the genome-wide array for the D. simulans-D. sechellia species pair, and from the larvae of these two species pairs using the custom array, are presented separately. Keywords: Comparison of pure-species Drosophila expression to hybrid expression
Project description:Species often produce sterile hybrids early in their evolutionary divergence, and some evidence suggests that hybrid sterility may be associated with deviations or disruptions in gene expression. In support of this idea, many studies have shown that a high proportion of male-biased genes are underexpressed compared to non-sex-biased genes in sterile F1 male hybrids of Drosophila species. In this study, we examined and compared patterns of misexpression in 4 day old sterile male F1 hybrids of Drosophila simulans and its sibling species, D. sechellia. We analyzed hybrids using genome-wide D. melanogaster arrays from the Drosophila Genome Resource Center (DGRC). The results from a custom array (GPL4022) for this species pair, from the custom array and the genome-wide array for the D. simulans-D. mauritiana species pair, and from the larvae of these two species pairs using the custom array, are presented separately. Keywords: Comparison of pure-species Drosophila expression to hybrid expression
Project description:The skin commensal yeast Malassezia is associated with several skin disorders. To establish a reference resource, we sought to determine the complete genome sequence of Malassezia sympodialis and identify its protein-coding genes. A novel genome annotation workflow combining RNA sequencing, proteomics, and manual curation was developed to determine gene structures with high accuracy.
Project description:Cytosine methylation in the genome of Drosophila melanogaster has been elusive and controversial: methylcytosine has been detected at very low levels in early embryos, but the genomic location and function of methylation has not been established. We have mapped cytosine methylation genomewide in Stage 5 Drosophila embryo DNA by combining immuno-enrichment for 5-methylcytosine, bisulfite conversion, and deep sequencing. Unlike methylation patterns observed in other eukaryotic species, methylation in Drosophila is punctate and highly strand-asymmetrical; we confirmed this by direct PCR amplification and sequencing of bisulfite-converted DNA. Despite the locally asymmetric nature of methylation, large-scale patterns of methylation are symmetric. Methylated regions make up ~1% of the genome, and within these regions methylation of individual cytosines averages 2-10%. Methylation is concentrated in specific 5-base sequence motifs that are CA- and CT-rich but depleted of guanine. It is depleted from promoters, coding sequences, and most retrotransposons, and enriched in introns and in certain simple sequence repeats containing the commonly methylated motifs. Comparison with available gene expression data indicates that methylation in a gene is associated with lower expression; the X chromosome, which is subject to gene dosage compensation, is more densely methylated than the autosomes. This study firmly establishes the presence of cytosine methylation in Drosophila; the temporal overlap of methylation with the maternal-zygotic transition raises the possibility that methylation participates in the transition to zygotic gene expression. To enrich for rare cytosine methylation in Drosophila at embryonic Stage 5 (2-3 hours post-fertilization), we enriched sonicated Stage 5 genomic DNA for methylcytosine by immunoprecipitation with antibody to 5-methylcytosine. The immunoprecipitated DNA was then bisulfite converted and Illumina sequenced to obtain direct evidence for the presence of methylation. The presence and extent of DNA methylation was confirmed by Illumina sequencing of bisulfite-converted PCR amplicons.
Project description:We compared the genome-wide expression profiles of two yeast species (S. cerevisiae and S. paradoxus) using a two-species microarray that contain species-specific probes and can thus measure the expression levels of the two species simultaneosly. In Addition, we used the array to measure expression levels of the interspecific hybrid of these yeast species, while discriminating between the alleles that correspond to the two parental species. Comparison of the between-species differences and the within-hybrid allele differences allows us to separate cis from trans effects. Also, comparison of the overall expression in the hybrids (both alleles) with their parental species allows us to analyze hybrid over-expression and under-expression. Keywords: comparative transcriptome analysis, hybrid gene expression
Project description:Species often produce sterile hybrids early in their evolutionary divergence, and some evidence suggests that hybrid sterility may be associated with deviations or disruptions in gene expression. In support of this idea, many studies have shown that a high proportion of male-biased genes are underexpressed compared to non-sex-biased genes in sterile F1 male hybrids of Drosophila species. In this study, we examined and compared patterns of misexpression in 4 day old sterile male F1 hybrids of Drosophila simulans and its sibling species, D. mauritiana. We analyzed hybrids using custom cDNA arrays we developed from RT-PCRs of spermatogenesis-related transcripts from these species and another sibling species (D. sechellia). The results from a commercial genome-wide array for this species pair, from the custom chip and the genome-wide chip for the D. simulans-D. sechellia species pair, and from the larvae of these two species pairs using the custom chip, is presented separately. Keywords: Comparison of pure-species Drosophila expression to hybrid expression