Integrating large-scale functional genomic data to dissect the complexity of yeast regulatory networks

Radiotherapy is one of the most important cancer treatments, but its response varies greatly among individual patients. Therefore, the prediction of radiosensitivity, identification of potential signature genes, and inference of their regulatory networks are important for clinical and oncological reasons. Here, we proposed a novel multiple genomic fused partial least squares deep regression method to simultaneously analyze multi-genomic data. Using 60 National Cancer Institute cell lines as examples, we aimed to identify signature genes by optimizing the radiosensitivity prediction model and uncovering regulatory relationships. A total of 113 signature genes were selected from more than 20,000 genes. The root mean square error of the model was only 0.0025, which was much lower than previously published results, suggesting that our method can predict radiosensitivity with the highest accuracy. Additionally, our regulatory network analysis identified 24 highly important ‘hub’ genes. The data analysis workflow we propose provides a unified and computational framework to harness the full potential of large-scale integrated cancer genomic data for integrative signature discovery. Furthermore, the regression model, signature genes, and their regulatory network should provide a reliable quantitative reference for optimizing personalized treatment options, and may aid our understanding of cancer progress mechanisms.

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Chinese Glioma Genome Atlas (CGGA): A Comprehensive Resource with Functional Genomic Data for Chinese Glioma Patients

10.1101/2020.01.20.911982 ◽

2020 ◽

Cited By ~ 3

Author(s):

Zheng Zhao ◽

Ke’nan Zhang ◽

Qiangwei Wang ◽

Guanzhang Li ◽

Fan Zeng ◽

...

Keyword(s):

Dna Methylation ◽

Survival Data ◽

Messenger Rna ◽

Genomic Data ◽

Biological Research ◽

Analysis Tool ◽

Functional Genomic ◽

Functional Genomic Data ◽

Who Grade ◽

Genome Atlas

AbstractGliomas are the most common and malignant intracranial tumours in adults. Recent studies have shown that functional genomics greatly aids in the understanding of the pathophysiology and therapy of glioma. However, comprehensive genomic data and analysis platforms are relatively limited. In this study, we developed the Chinese Glioma Genome Atlas (CGGA, http://www.cgga.org.cn), a user-friendly data portal for storage and interactive exploration of multi-dimensional functional genomic data that includes nearly 2,000 primary and recurrent glioma samples from Chinese cohorts. CGGA currently provides access to whole-exome sequencing (286 samples), messenger RNA sequencing (1,018 samples) and microarray (301 samples), DNA methylation microarray (159 samples), and microRNA microarray (198 samples) data, as well as detailed clinical data (e.g., WHO grade, histological type, critical molecular genetic information, age, sex, chemoradiotherapy status and survival data). In addition, we developed an analysis tool to allow users to browse mutational, mRNA/microRNA expression, and DNA methylation profiles and perform survival and correlation analyses of specific glioma subtypes. CGGA greatly reduces the barriers between complex functional genomic data and glioma researchers who seek rapid, intuitive, and high-quality access to data resources and enables researchers to use these immeasurable data sources for biological research and clinical application. Importantly, the free provision of data will allow researchers to quickly generate and provide data to the research community.

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Pairwise comparisons across species are problematic when analyzing functional genomic data

10.1101/107177 ◽

2017 ◽

Cited By ~ 4

Author(s):

Casey W. Dunn ◽

Felipe Zapata ◽

Catriona Munro ◽

Stefan Siebert ◽

Andreas Hejnol

Keyword(s):

Gene Expression ◽

Evolutionary Process ◽

Opportunity To Learn ◽

Genomic Data ◽

The Other ◽

Evolutionary Relationships ◽

Pairwise Comparisons ◽

Functional Genomic ◽

Functional Genomic Data ◽

Comparative Functional Genomics

AbstractThere is considerable interest in comparing functional genomic data across species. One goal of such work is to provide an integrated understanding of genome and phenotype evolution. Most comparative functional genomic studies have relied on multiple pairwise comparisons between species, an approach that does not incorporate information about the evolutionary relationships among species. The statistical problems that arise from not considering these relationships can lead pairwise approaches to the wrong conclusions, and are a missed opportunity to learn about biology that can only be understood in an explicit phylogenetic context. Here we examine two recently published studies that compare gene expression across species with pairwise methods, and find reason to question the original conclusions of both. One study interpreted pairwise comparisons of gene expression as support for the ortholog conjecture, the hypothesis that orthologs tend to be more similar than paralogs. The other study interpreted pairwise comparisons of embryonic gene expression across distantly related animals as evidence for a distinct evolutionary process that gave rise to phyla. In each study, distinct patterns of pairwise similarity among species were originally interpreted as evidence of particular evolutionary processes, but instead we find they reflect species relationships. These reanalyses concretely demonstrate the inadequacy of pairwise comparisons for analyzing functional genomic data across species. It will be critical to adopt phylogenetic comparative methods in future functional genomic work. Fortunately, phylogenetic comparative biology is also a rapidly advancing field with many methods that can be directly applied to functional genomic data.SignificanceComparisons of genome function between species are providing important insight into the evolutionary origins of diversity. Here we demonstrate that comparative functional genomics studies can come to the wrong conclusions if they do not take the relationships of species into account and instead rely on pairwise comparisons between species, as is common practice. We re-examined two previously published studies and found problems with pairwise comparisons that draw both their original conclusions into question. One study had found support for the ortholog conjecture and the other had concluded that the evolution of gene expression was different between animal phyla than within them. Our results demonstrate that to answer evolutionary questions about genome function, it is critical to consider evolutionary relationships.

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Continuous-trait probabilistic model for comparing multi-species functional genomic data

10.1101/283093 ◽

2018 ◽

Author(s):

Yang Yang ◽

Quanquan Gu ◽

Yang Zhang ◽

Takayo Sasaki ◽

Julianna Crivello ◽

...

Keyword(s):

Comparative Analysis ◽

Molecular Mechanisms ◽

Probabilistic Models ◽

Phenotypic Diversity ◽

Genomic Data ◽

Primate Species ◽

Functional Genomic ◽

Functional Genomic Data ◽

Continuous Trait ◽

A Genome

SummaryA large amount of multi-species functional genomic data from high-throughput assays are becoming available to help understand the molecular mechanisms for phenotypic diversity across species. However, continuous-trait probabilistic models, which are key to such comparative analysis, remain underexplored. Here we develop a new model, called phylogenetic hidden Markov Gaussian processes (Phylo-HMGP), to simultaneously infer heterogeneous evolutionary states of functional genomic features in a genome-wide manner. Both simulation studies and real data application demonstrate the effectiveness of Phylo-HMGP. Importantly, we applied Phylo-HMGP to analyze a new cross-species DNA replication timing (RT) dataset from the same cell type in five primate species (human, chimpanzee, orangutan, gibbon, and green monkey). We demonstrate that our Phylo-HMGP model enables discovery of genomic regions with distinct evolutionary patterns of RT. Our method provides a generic framework for comparative analysis of multi-species continuous functional genomic signals to help reveal regions with conserved or lineage-specific regulatory roles.

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Continuous-Trait Probabilistic Model for Comparing Multi-species Functional Genomic Data

Cell Systems ◽

10.1016/j.cels.2018.05.022 ◽

2018 ◽

Vol 7 (2) ◽

pp. 208-218.e11 ◽

Cited By ~ 8

Author(s):

Yang Yang ◽

Quanquan Gu ◽

Yang Zhang ◽

Takayo Sasaki ◽

Julianna Crivello ◽

...

Keyword(s):

Probabilistic Model ◽

Genomic Data ◽

Functional Genomic ◽

Functional Genomic Data ◽

Continuous Trait

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Pairwise comparisons across species are problematic when analyzing functional genomic data

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1707515115 ◽

2018 ◽

Vol 115 (3) ◽

pp. E409-E417 ◽

Cited By ~ 40

Author(s):

Casey W. Dunn ◽

Felipe Zapata ◽

Catriona Munro ◽

Stefan Siebert ◽

Andreas Hejnol

Keyword(s):

Gene Expression ◽

Evolutionary Process ◽

Opportunity To Learn ◽

Genomic Data ◽

Pairwise Comparisons ◽

Functional Genomic ◽

Functional Genomic Data ◽

Genomic Studies ◽

Compare Gene Expression ◽

Missed Opportunity

There is considerable interest in comparing functional genomic data across species. One goal of such work is to provide an integrated understanding of genome and phenotype evolution. Most comparative functional genomic studies have relied on multiple pairwise comparisons between species, an approach that does not incorporate information about the evolutionary relationships among species. The statistical problems that arise from not considering these relationships can lead pairwise approaches to the wrong conclusions and are a missed opportunity to learn about biology that can only be understood in an explicit phylogenetic context. Here, we examine two recently published studies that compare gene expression across species with pairwise methods, and find reason to question the original conclusions of both. One study interpreted pairwise comparisons of gene expression as support for the ortholog conjecture, the hypothesis that orthologs tend to have more similar attributes (expression in this case) than paralogs. The other study interpreted pairwise comparisons of embryonic gene expression across distantly related animals as evidence for a distinct evolutionary process that gave rise to phyla. In each study, distinct patterns of pairwise similarity among species were originally interpreted as evidence of particular evolutionary processes, but instead, we find that they reflect species relationships. These reanalyses concretely show the inadequacy of pairwise comparisons for analyzing functional genomic data across species. It will be critical to adopt phylogenetic comparative methods in future functional genomic work. Fortunately, phylogenetic comparative biology is also a rapidly advancing field with many methods that can be directly applied to functional genomic data.

Download Full-text