Abstract:
:Tumorigenesis is a multi-step process, involving the acquisition of multiple oncogenic mutations that transform cells, resulting in systemic dysregulation that enables proliferation, invasion, and other cancer hallmarks. The goal of precision medicine is to identify therapeutically-actionable mutations from large-scale omic datasets. However, the multiplicity of oncogenes required for transformation, known as oncogenic collaboration, makes assigning effective treatments difficult. Motivated by this observation, we propose a new type of oncogenic collaboration where mutations in genes that interact with an oncogene may contribute to the oncogene's deleterious potential, a new genomic feature that we term "surrogate oncogenes." Surrogate oncogenes are representatives of these mutated subnetworks that interact with oncogenes. By mapping mutations to a protein-protein interaction network, we determine the significance of the observed distribution using permutation-based methods. For a panel of 38 breast cancer cell lines, we identified a significant number of surrogate oncogenes in known oncogenes such as BRCA1 and ESR1, lending credence to this approach. In addition, using Random Forest Classifiers, we show that these significant surrogate oncogenes predict drug sensitivity for 74 drugs in the breast cancer cell lines with a mean error rate of 30.9%. Additionally, we show that surrogate oncogenes are predictive of survival in patients. The surrogate oncogene framework incorporates unique or rare mutations from a single sample, and therefore has the potential to integrate patient-unique mutations into drug sensitivity predictions, suggesting a new direction in precision medicine and drug development. Additionally, we show the prevalence of significant surrogate oncogenes in multiple cancers from The Cancer Genome Atlas, suggesting that surrogate oncogenes may be a useful genomic feature for guiding pancancer analyses and assigning therapies across many tissue types.
journal_name
Front Genetjournal_title
Frontiers in geneticsauthors
Laderas TG,Heiser LM,Sönmez Kdoi
10.3389/fgene.2015.00341subject
Has Abstractpub_date
2015-12-23 00:00:00pages
341issn
1664-8021journal_volume
6pub_type
杂志文章abstract::Successful seedling establishment depends on the optimum depth of seed placement especially in drought-prone conditions, providing an opportunity to exploit subsoil water and increase winter survival in winter wheat. Coleoptile length is a key determinant for the appropriate depth at which seed can be sown. Thus, unde...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2019.01345
更新日期:2020-02-05 00:00:00
abstract::In recent years, studies have shown that phytopathogenic fungi possess the ability of cross-kingdom regulation of host plants through small RNAs (sRNAs). Magnaporthe oryzae, a causative agent of rice blast, introduces disease by penetrating the rice tissues through appressoria. However, little is known about the trans...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2019.00296
更新日期:2019-03-29 00:00:00
abstract::Communication disorders have complex genetic origins, with constellations of relevant gene markers that vary across individuals. Some genetic variants are present in healthy individuals as well as those affected by developmental disorders. Growing evidence suggests that some variants may increase susceptibility to the...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2015.00272
更新日期:2015-08-24 00:00:00
abstract::Different genes have their protein products localized in various subcellular compartments. The diversity in protein localization may serve as a gene characteristic, revealing gene essentiality from a subcellular perspective. To measure this diversity, we introduced a Subcellular Diversity Index (SDI) based on the Gene...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2019.01342
更新日期:2020-01-21 00:00:00
abstract:Background:Recent evidence has indicated that long non-coding RNAs (lncRNAs) can function as competing endogenous RNAs (ceRNAs) to modulate mRNAs expression by sponging microRNAs (miRNAs). However, the specific mechanism and function of lncRNA-miRNA-mRNA regulatory network in non-small cell lung cancer (NSCLC) remains ...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2020.511676
更新日期:2020-09-18 00:00:00
abstract::Functional annotation of the genome is important to understand the phenotypic complexity of various species. The road toward functional annotation involves several challenges ranging from experiments on individual molecules to large-scale analysis of high-throughput sequencing (HTS) data. HTS data is typically a resul...
journal_title:Frontiers in genetics
pub_type: 杂志文章,评审
doi:10.3389/fgene.2015.00188
更新日期:2015-05-19 00:00:00
abstract::The mammalian hearing organ is a regular array of two types of hair cells (HCs) surrounded by six types of supporting cells. Along the tonotopic axis, this conserved radial array of cell types shows longitudinal variations to enhance the tuning properties of basilar membrane. We present the current evidence supporting...
journal_title:Frontiers in genetics
pub_type: 杂志文章,评审
doi:10.3389/fgene.2018.00156
更新日期:2018-05-08 00:00:00
abstract::Somatic alterations in the epidermal growth factor receptor gene (EGFR) result in aberrant activation of kinase signaling and occur in ∼15% of non-small cell lung cancers (NSCLC). Patients diagnosed with EGFR-mutant NSCLC have good initial clinical response to EGFR tyrosine kinase inhibitors (EGFR TKIs), yet tumor rec...
journal_title:Frontiers in genetics
pub_type: 杂志文章,评审
doi:10.3389/fgene.2020.00281
更新日期:2020-03-27 00:00:00
abstract::The diagnosis of mesothelioma is not always straightforward, despite known immunohistochemical markers and other diagnostic techniques. One reason for the difficulty is that extrapleural tumors resembling mesothelioma may have several possible etiologies, especially in cases with no meaningful history of amphibole asb...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2014.00151
更新日期:2014-05-30 00:00:00
abstract::Background: Sturgeons (Chondrostei: Acipenseridae) are a group of "living fossil" fishes at a basal position among Actinopteri. They have raised great public interest due to their special evolutionary position, species conservation challenges, as well as their highly-prized eggs (caviar). The sterlet, Acipenser ruthen...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2019.00776
更新日期:2019-09-05 00:00:00
abstract::DNA methylation is an indispensable epigenetic modification that dynamically regulates gene expression and genome stability during cell growth and development processes. The target of rapamycin (TOR) has emerged as a central regulator to regulate many fundamental cellular metabolic processes from protein synthesis to ...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2020.00186
更新日期:2020-03-03 00:00:00
abstract::von Hippel-Lindau (VHL) disease is a hereditary cancer syndrome with poor survival. The current recommendations have proposed uniform surveillance strategies for all patients, neglecting the obvious phenotypic varieties. In this study, we aim to confirm the phenotypic heterogeneity in VHL disease and the underlying me...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2019.00358
更新日期:2019-04-24 00:00:00
abstract::The microbiome is known to have a profound effect on the development, physiology and health of its host. Whether and how it also contributes to evolutionary diversification of the host is, however, unclear. Here we hypothesize that disruption of the microbiome by new stressful environments interferes with host-microbe...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2014.00168
更新日期:2014-06-20 00:00:00
abstract::Although bipolar disorder (BP) is one of the most heritable psychiatric conditions, susceptibility genes for the disorder have yet to be conclusively identified. It is likely that variants in multiple genes across multiple pathways contribute to the genotype-phenotype relationship in the affected population. Recent ev...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2013.00105
更新日期:2013-06-11 00:00:00
abstract::Fragile X syndrome (FXS) is mostly caused by two distinct events that occur in the FMR1 gene (Xq27.3): an expansion above 200 repeats of a CGG triplet located in the 5'UTR of the gene, and methylation of the cytosines located in the CpG islands upstream of the CGG repeats. Here, we describe two unrelated families with...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2018.00442
更新日期:2018-11-02 00:00:00
abstract::Background: The aim of this study was to explore the Human Papillomavirus (HPV) genotype composition and intra-genotype variants within individual samples of low- and high-grade cervical cytology by deep sequencing. Clinical, cytological, sequencing, and functional/structural data were forged into an integrated varian...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2019.00489
更新日期:2019-05-24 00:00:00
abstract::Lactation is a dynamic process, which evolved to meet dietary demands of growing offspring. At the same time, the mother's metabolism changes to meet the high requirements of nutrient supply to the offspring. Through strong artificial selection, the strain of milk production on dairy cows is often associated with impa...
journal_title:Frontiers in genetics
pub_type: 杂志文章,评审
doi:10.3389/fgene.2015.00118
更新日期:2015-03-26 00:00:00
abstract::Gene copy-number differences due to gene duplications and deletions are rampant in natural populations and play a crucial role in the evolution of genome complexity. Per-locus analyses of gene duplication rates in the pre-genomic era revealed that gene duplication rates are much higher than the per nucleotide substitu...
journal_title:Frontiers in genetics
pub_type: 杂志文章,评审
doi:10.3389/fgene.2013.00273
更新日期:2013-12-10 00:00:00
abstract::Inference of absolute copy numbers in tumor genomes is one of the key points in the study of tumor genesis. However, the mixture of tumor and normal cells poses a big challenge to this task. Accurate estimation of tumor purity (i.e., the fraction of tumor cells) is a necessary step to solve this problem. In this paper...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2020.00458
更新日期:2020-04-30 00:00:00
abstract::We evaluated differences in gene expression in pigs from the Porcine Reproductive and Respiratory Syndrome (PRRS) Host Genetics Consortium initiative showing a range of responses to PRRS virus infection. Pigs were allocated into four phenotypic groups according to their serum viral level and weight gain. RNA obtained ...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2012.00321
更新日期:2013-01-16 00:00:00
abstract::The megadiversity of the neotropical ichthyofauna has been associated to recent diversification processes, reflecting in subtle or lacking morphological differentiation between species, challenging the classical taxonomic identification. Leporinus friderici occurs in several river basins of South America, and its nomi...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2018.00047
更新日期:2018-02-15 00:00:00
abstract::Colon cancer has the third highest incidence and mortality among cancers in the United States. MicroRNA-21 (miR21) has been described as an oncomir that is highly overexpressed in tumor tissue from colorectal cancer. Recent studies showed that silencing of miR21 through use of a miR21 inhibitor (anti-miR21) affected v...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2013.00301
更新日期:2014-01-02 00:00:00
abstract:Background:SOX2 overlapping transcript (SOX2-OT) produces alternatively spliced long non-coding RNAs (lncRNA). Previous studies of the prognostic role of SOX2-OT expression met with conflicting results. The aim of this study was to properly consider the prognostic role of SOX2-OT expression in several cancers. In addit...
journal_title:Frontiers in genetics
pub_type:
doi:10.3389/fgene.2019.01375
更新日期:2020-01-23 00:00:00
abstract::Sertoli cells are central and essential coordinators of spermatogenesis. Accumulating evidence has demonstrated that miRNAs participate in the regulation of Sertoli cell growth. However, the functions and the regulatory mechanisms of miRNAs in Sertoli cells of domestic animals remain largely unknown. Here we report th...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2020.581593
更新日期:2020-10-29 00:00:00
abstract::Muscle weakness is a common consequence of both aging (sarcopenia) and neuromuscular disorders (NMD). Whilst genome-wide association (GWA) studies have identified genetic variants associated with grip strength (GS; measure of muscle strength/weakness) and NMDs, including multiple sclerosis (MS), myasthenia gravis (MG)...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2020.00393
更新日期:2020-04-24 00:00:00
abstract::Background: Porcine respiratory and reproductive syndrome virus (PRRSV) is a single-stranded RNA virus member that infects pigs and causes losses to the commercial industry reaching upward of a billion dollars annually in combined direct and indirect costs. The virus can be separated into etiologies that contain multi...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2019.00691
更新日期:2019-08-02 00:00:00
abstract::Tools for genomic island prediction use strategies for genomic comparison analysis and sequence composition analysis. The goal of comparative analysis is to identify unique regions in the genomes of related organisms, whereas sequence composition analysis evaluates and relates the composition of specific regions with ...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2018.00619
更新日期:2018-12-12 00:00:00
abstract::As one of the hotspot regions for sympatric speciation studies, Evolution Canyon (EC) became an ideal place for its high level of microclimatic divergence interslopes. In this study, to highlight the genetic mechanisms of sympatric speciation, phenotypic variation on flowering time and transcriptomic divergence were i...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2018.00506
更新日期:2018-11-14 00:00:00
abstract::The New England Centenarian Study (NECS) was founded in 1994 as a longitudinal study of centenarians to determine if centenarians could be a model of healthy human aging. Over time, the NECS along with other centenarian studies have demonstrated that the majority of centenarians markedly delay high mortality risk-asso...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2012.00277
更新日期:2012-11-30 00:00:00
abstract::STI/HOP functions as a co-chaperone of HSP90 and HSP70 whose molecular function has largely been being restricted as an adaptor protein. However, its role in thermotolerance is not well explored. In this article, we have identified six members of the TaSTI family, which were named according to their distribution on gr...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2020.00873
更新日期:2020-08-19 00:00:00