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1.
Commun Biol ; 4(1): 1194, 2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34663927

RESUMO

The selection of peptides presented by MHC molecules is crucial for antigen discovery. Previously, several predictors have shown impressive performance on binding affinity. However, the decisive MHC residues and their relation to the selection of binding peptides are still unrevealed. Here, we connected HLA alleles with binding motifs via our deep learning-based framework, MHCfovea. MHCfovea expanded the knowledge of MHC-I-binding motifs from 150 to 13,008 alleles. After clustering N-terminal and C-terminal sub-motifs on both observed and unobserved alleles, MHCfovea calculated the hyper-motifs and the corresponding allele signatures on the important positions to disclose the relation between binding motifs and MHC-I sequences. MHCfovea delivered 32 pairs of hyper-motifs and allele signatures (HLA-A: 13, HLA-B: 12, and HLA-C: 7). The paired hyper-motifs and allele signatures disclosed the critical polymorphic residues that determine the binding preference, which are believed to be valuable for antigen discovery and vaccine design when allele specificity is concerned.

2.
J Econ Entomol ; 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34462779

RESUMO

Several species of drywood termites, subterranean termites, and fungus-growing termites cause extensive economic losses annually worldwide. Because no universal method is available for controlling all termites, correct species identification is crucial for termite management. Despite deep neural network technologies' promising performance in pest recognition, a method for automatic termite recognition remains lacking. To develop an automated deep learning classifier for termite image recognition suitable for mobile applications, we used smartphones to acquire 18,000 original images each of four termite pest species: Kalotermitidae: Cryptotermes domesticus (Haviland); Rhinotermitidae: Coptotermes formosanus Shiraki and Reticulitermes flaviceps (Oshima); and Termitidae: Odontotermes formosanus (Shiraki). Each original image included multiple individuals, and we applied five image segmentation techniques for capturing individual termites. We used 24,000 individual-termite images (4 species × 2 castes × 3 groups × 1,000 images) for model development and testing. We implemented a termite classification system by using a deep learning-based model, MobileNetV2. Our models achieved high accuracy scores of 0.947, 0.946, and 0.929 for identifying soldiers, workers, and both castes, respectively, which is not significantly different from human expert performance. We further applied image augmentation techniques, including geometrical transformations and intensity transformations, to individual-termite images. The results revealed that the same classification accuracy can be achieved by using 1,000 augmented images derived from only 200 individual-termite images, thus facilitating further model development on the basis of many fewer original images. Our image-based identification system can enable the selection of termite control tools for pest management professionals or homeowners.

3.
Theranostics ; 11(16): 7779-7796, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335964

RESUMO

Rationale: The progression of prostate cancer (PCa) to castration-resistant PCa (CRPC) despite continuous androgen deprivation therapy is a major clinical challenge. Over 90% of patients with CRPC exhibit sustained androgen receptor (AR) signaling. KDM4B that removes the repressive mark H3K9me3/2 is a transcriptional activator of AR and has been implicated in the development of CRPC. However, the mechanisms of KDM4B involvement in CRPC remain largely unknown. Here, we sought to demonstrate the molecular pathway mediated by KDM4B in CRPC and to provide proof-of-concept evidence that KDM4B is a potential CRPC target. Methods: CRPC cells (C4-2B or CWR22Rv1) depleted with KDM4B followed by cell proliferation (in vitro and xenograft), microarray, qRT-PCR, Seahorse Flux, and metabolomic analyses were employed to identify the expression and metabolic profiles mediated by KDM4B. Immunoprecipitation was used to determine the KDM4B-c-Myc interaction region. Reporter activity assay and ChIP analysis were used to characterize the KDM4B-c-Myc complex-mediated mechanistic actions. The clinical relevance between KDM4B and c-Myc was determined using UCSC Xena analysis and immunohistochemistry. Results: We showed that KDM4B knockdown impaired CRPC proliferation, switched Warburg to OXPHOS metabolism, and suppressed gene expressions including those targeted by c-Myc. We further demonstrated that KDM4B physically interacted with c-Myc and they were co-recruited to the c-Myc-binding sequence on the promoters of metabolic genes (LDHA, ENO1, and PFK). Importantly, KDM4B and c-Myc synergistically promoted the transactivation of the LDHA promoter in a demethylase-dependent manner. We also provided evidence that KDM4B and c-Myc are co-expressed in PCa tissue and that high expression of both is associated with worse clinical outcome. Conclusions: KDM4B partners with c-Myc and serves as a coactivator of c-Myc to directly enhance c-Myc-mediated metabolism, hence promoting CRPC progression. Targeting KDM4B is thus an alternative therapeutic strategy for advanced prostate cancers driven by c-Myc and AR.


Assuntos
Histona Desmetilases com o Domínio Jumonji/metabolismo , Neoplasias de Próstata Resistentes à Castração/metabolismo , Antagonistas de Androgênios , Animais , Linhagem Celular Tumoral , Proliferação de Células/genética , Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/genética , Xenoenxertos , Humanos , Histona Desmetilases com o Domínio Jumonji/fisiologia , Masculino , Camundongos Endogâmicos BALB C , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/patologia , Receptores Androgênicos/metabolismo , Transdução de Sinais/genética , Fatores de Transcrição/metabolismo
4.
Nucleic Acids Res ; 49(13): 7318-7329, 2021 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-34197604

RESUMO

Integrating omics data with quantification of biological traits provides unparalleled opportunities for discovery of genetic regulators by in silico inference. However, current approaches to analyze genetic-perturbation screens are limited by their reliance on annotation libraries for prioritization of hits and subsequent targeted experimentation. Here, we present iTARGEX (identification of Trait-Associated Regulatory Genes via mixture regression using EXpectation maximization), an association framework with no requirement of a priori knowledge of gene function. After creating this tool, we used it to test associations between gene expression profiles and two biological traits in single-gene deletion budding yeast mutants, including transcription homeostasis during S phase and global protein turnover. For each trait, we discovered novel regulators without prior functional annotations. The functional effects of the novel candidates were then validated experimentally, providing solid evidence for their roles in the respective traits. Hence, we conclude that iTARGEX can reliably identify novel factors involved in given biological traits. As such, it is capable of converting genome-wide observations into causal gene function predictions. Further application of iTARGEX in other contexts is expected to facilitate the discovery of new regulators and provide observations for novel mechanistic hypotheses regarding different biological traits and phenotypes.


Assuntos
Perfilação da Expressão Gênica , Genes Reguladores , Proteólise , Fase S/genética , Software , Transcrição Genética , Proteínas de Transporte/genética , Biologia Computacional/métodos , Replicação do DNA , Deleção de Genes , Homeostase , Mutação , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genética
5.
FEBS Lett ; 594(10): 1477-1496, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32052437

RESUMO

Eukaryotic transcription factors (TFs) coordinate different upstream signals to regulate the expression of their target genes. To unveil this regulatory network in B-cell receptor signaling, we developed a computational pipeline to systematically analyze the extracellular signal-regulated kinase (ERK)- and IκB kinase (IKK)-dependent transcriptome responses. We combined a bilinear regression method and kinetic modeling to identify the signal-to-TF and TF-to-gene dynamics, respectively. We input a set of time-course experimental data for B cells and concentrated on transcriptional activators. The results show that the combination of TFs differentially controlled by ERK and IKK could contribute divergent expression dynamics in orchestrating the B-cell response. Our findings provide insights into the regulatory mechanisms underlying signal-dependent gene expression in eukaryotic cells.


Assuntos
Simulação por Computador , Regulação da Expressão Gênica , Transdução de Sinais/genética , Transcrição Genética , Animais , Biocatálise , Galinhas/genética , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Redes Reguladoras de Genes , Quinase I-kappa B/metabolismo , Modelos Biológicos , Receptores de Antígenos de Linfócitos B/metabolismo , Fatores de Transcrição/metabolismo
6.
Nat Commun ; 11(1): 809, 2020 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-32041946

RESUMO

Transcription-replication conflicts (TRCs) occur when intensive transcriptional activity compromises replication fork stability, potentially leading to gene mutations. Transcription-deposited H3K4 methylation (H3K4me) is associated with regions that are susceptible to TRCs; however, the interplay between H3K4me and TRCs is unknown. Here we show that H3K4me aggravates TRC-induced replication failure in checkpoint-defective cells, and the presence of methylated H3K4 slows down ongoing replication. Both S-phase checkpoint activity and H3K4me are crucial for faithful DNA synthesis under replication stress, especially in highly transcribed regions where the presence of H3K4me is highest and TRCs most often occur. H3K4me mitigates TRCs by decelerating ongoing replication, analogous to how speed bumps slow down cars. These findings establish the concept that H3K4me defines the transcriptional status of a genomic region and defends the genome from TRC-mediated replication stress and instability.


Assuntos
Replicação do DNA , Histonas/metabolismo , Transcrição Genética , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Quinase do Ponto de Checagem 2/genética , Quinase do Ponto de Checagem 2/metabolismo , Cromatina/metabolismo , DNA Polimerase II/metabolismo , Genoma Fúngico/genética , Instabilidade Genômica , Histona-Lisina N-Metiltransferase/metabolismo , Histonas/genética , Metilação , Modelos Genéticos , Mutação , Pontos de Checagem da Fase S do Ciclo Celular/genética , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo
8.
Nucleic Acids Res ; 47(10): 5181-5192, 2019 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-30918956

RESUMO

Eukaryotic cells pack their genomic DNA into euchromatin and heterochromatin. Boundaries between these domains have been shown to be set by boundary elements. In Tetrahymena, heterochromatin domains are targeted for deletion from the somatic nuclei through a sophisticated programmed DNA rearrangement mechanism, resulting in the elimination of 34% of the germline genome in ∼10,000 dispersed segments. Here we showed that most of these deletions occur consistently with very limited variations in their boundaries among inbred lines. We identified several potential flanking regulatory sequences, each associated with a subset of deletions, using a genome-wide motif finding approach. These flanking sequences are inverted repeats with the copies located at nearly identical distances from the opposite ends of the deleted regions, suggesting potential roles in boundary determination. By removing and testing two such inverted repeats in vivo, we found that the ability for boundary maintenance of the associated deletion were lost. Furthermore, we analyzed the deletion boundaries in mutants of a known boundary-determining protein, Lia3p and found that the subset of deletions that are affected by LIA3 knockout contained common features of flanking regulatory sequences. This study suggests a common mechanism for setting deletion boundaries by flanking inverted repeats in Tetrahymena thermophila.


Assuntos
DNA de Protozoário/genética , Deleção de Genes , Heterocromatina/química , Proteínas de Protozoários/genética , Tetrahymena thermophila/genética , Motivos de Aminoácidos , Núcleo Celular/metabolismo , DNA de Protozoário/metabolismo , Eucromatina/química , Regulação da Expressão Gênica , Rearranjo Gênico , Genoma de Protozoário , Domínios Proteicos
9.
Bioinformatics ; 35(8): 1414-1415, 2019 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-30202999

RESUMO

SUMMARY: In higher eukaryotes, the generation of transcript isoforms from a single gene through alternative splicing (AS) and alternative transcription (AT) mechanisms increases functional and regulatory diversities. Annotating these alternative transcript events is essential for genomic studies. However, there are no existing tools that generate comprehensive annotations of all these alternative transcript events including both AS and AT events. In the present study, we develop CATANA, with the encoded exon usage patterns based on the flattened gene model, to identify ten types of AS and AT events. We demonstrate the power and versatility of CATANA by showing greater depth of annotations of alternative transcript events according to either genome annotation or RNA-seq data. AVAILABILITY AND IMPLEMENTATION: CATANA is available on https://github.com/shiauck/CATANA. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Processamento Alternativo , Software , Transcrição Genética , Éxons , Genoma , Análise de Sequência de RNA
10.
Front Genet ; 9: 571, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30524473

RESUMO

Changes in cis-regulatory DNA sequences and transcription factor (TF) repertoires provide major sources of phenotypic diversity that shape the evolution of gene regulation in eukaryotes. The DNA-binding specificities of TFs may be diversified or produce new variants in different eukaryotic species. However, it is currently unclear how various levels of divergence in TF DNA-binding specificities or motifs became introduced into the cis-regulatory DNA regions of the genome over evolutionary time. Here, we first estimated the evolutionary divergence levels of TF binding motifs and quantified their occurrence at DNase I-hypersensitive sites. Results from our in silico motif scan and experimentally derived chromatin immunoprecipitation (TF-ChIP) show that the divergent motifs tend to be introduced in the edges of cis-regulatory regions, which is probably accompanied by the expansion of the accessible core of promoter-associated regulatory elements during evolution. We also find that the genes neighboring the expanded cis-regulatory regions with the most divergent motifs are associated with functions like development and morphogenesis. Accordingly, we propose that the accumulation of divergent motifs in the edges of cis-regulatory regions provides a functional mechanism for the evolution of divergent regulatory circuits.

12.
BMC Genomics ; 18(1): 786, 2017 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-29037146

RESUMO

BACKGROUND: The regulatory roles of long intergenic noncoding RNAs (lincRNAs) in humans have been revealed through the use of advanced sequencing technology. Recently, three possible scenarios of lincRNA origins have been proposed: de novo origination from intergenic regions, duplication from other long noncoding RNAs, and pseudogenization from protein-coding genes. The first two scenarios are largely studied and supported, yet few studies focused on the evolution from pseudogenized protein-coding sequence to lincRNA. Due to the non-mutually exclusive nature of these three scenarios and the need of systematic investigation of lincRNA origination, we conducted a comparative genomics study to investigate the evolution of human lincRNAs. RESULTS: Combining with syntenic analysis and stringent Blastn e-value cutoff, we found that the majority of lincRNAs are aligned to intergenic regions of other species. Interestingly, 193 human lincRNAs could have protein-coding orthologs in at least two of nine vertebrates. Transposable elements in these conserved regions in human genome are much less than expectation. Moreover, 19% of these lincRNAs have overlaps with or are close to pseudogenes in the human genome. CONCLUSIONS: We suggest that a notable portion of lincRNAs could be derived from pseudogenized protein-coding genes. Furthermore, based on our computational analysis, we hypothesize that a subset of these lincRNAs could have potential to regulate their paralogs by functioning as competing endogenous RNAs. Our results provide evolutionary evidence of the relationship between human lincRNAs and protein-coding genes.


Assuntos
Genômica , Pseudogenes/genética , RNA Longo não Codificante/genética , Animais , Elementos de DNA Transponíveis/genética , Evolução Molecular , Genoma Humano/genética , Humanos , Anotação de Sequência Molecular , Homologia de Sequência do Ácido Nucleico
13.
PLoS Comput Biol ; 11(8): e1004418, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26291518

RESUMO

Transcription factor (TF) binding is determined by the presence of specific sequence motifs (SM) and chromatin accessibility, where the latter is influenced by both chromatin state (CS) and DNA structure (DS) properties. Although SM, CS, and DS have been used to predict TF binding sites, a predictive model that jointly considers CS and DS has not been developed to predict either TF-specific binding or general binding properties of TFs. Using budding yeast as model, we found that machine learning classifiers trained with either CS or DS features alone perform better in predicting TF-specific binding compared to SM-based classifiers. In addition, simultaneously considering CS and DS further improves the accuracy of the TF binding predictions, indicating the highly complementary nature of these two properties. The contributions of SM, CS, and DS features to binding site predictions differ greatly between TFs, allowing TF-specific predictions and potentially reflecting different TF binding mechanisms. In addition, a "TF-agnostic" predictive model based on three DNA "intrinsic properties" (in silico predicted nucleosome occupancy, major groove geometry, and dinucleotide free energy) that can be calculated from genomic sequences alone has performance that rivals the model incorporating experiment-derived data. This intrinsic property model allows prediction of binding regions not only across TFs, but also across DNA-binding domain families with distinct structural folds. Furthermore, these predicted binding regions can help identify TF binding sites that have a significant impact on target gene expression. Because the intrinsic property model allows prediction of binding regions across DNA-binding domain families, it is TF agnostic and likely describes general binding potential of TFs. Thus, our findings suggest that it is feasible to establish a TF agnostic model for identifying functional regulatory regions in potentially any sequenced genome.


Assuntos
Cromatina/química , DNA Fúngico/química , DNA Fúngico/metabolismo , Proteínas Fúngicas/metabolismo , Motivos de Nucleotídeos/genética , Saccharomyces cerevisiae/genética , Fatores de Transcrição/metabolismo , Cromatina/genética , Cromatina/metabolismo , Biologia Computacional , DNA Fúngico/genética , Proteínas Fúngicas/química , Proteínas Fúngicas/genética , Ligação Proteica , Fatores de Transcrição/química , Fatores de Transcrição/genética
14.
Sci Rep ; 5: 12648, 2015 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-26219400

RESUMO

Enhancers play a crucial role in gene regulation but the participation of enhancer transcripts (i.e. enhancer RNA, eRNAs) in regulatory systems remains unclear. We provide a computational analysis on eRNAs using genome-wide data across 12 mouse tissues. The expression of genes targeted by transcribing enhancer is positively correlated with eRNA expression and significantly higher than expression of genes targeted by non-transcribing enhancers. This result implies eRNA transcription indicates a state of enhancer that further increases gene expression. This state of enhancer is tissue-specific, as the same enhancer differentially transcribes eRNAs across tissues. Therefore, the presence of eRNAs describes a tissue-specific state of enhancer that is generally associated with higher expressed target genes, surmising as to whether eRNAs have gene activation potential. We further found a large number of eRNAs contain regions in which sequences and secondary structures are similar to microRNAs. Interestingly, an increasing number of recent studies hypothesize that microRNAs may switch from their general repressive role to an activating role when targeting promoter sequences. Collectively, our results provide speculation that eRNAs may be associated with the selective activation of enhancer target genes.


Assuntos
Elementos Facilitadores Genéticos/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Genoma/genética , RNA/genética , Animais , Camundongos , MicroRNAs/genética , Especificidade de Órgãos/genética , Regiões Promotoras Genéticas/genética , Transcrição Genética
15.
Mol Microbiol ; 97(6): 1128-41, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26082024

RESUMO

Helicobacter pylori inhabits the gastric mucosa where it senses and responds to various stresses via a two-component systems (TCSs) that enable its persistent colonization. The aim of this study was to investigate whether any of the three paired TCSs (ArsRS, FleRS and CrdRS) in H. pylori respond to nitrosative stress. The results showed that the expression of crdS was significantly increased upon exposure to nitric oxide (NO). crdS-knockout (ΔcrdS) and crdR/crdS-knockout (ΔcrdRS) H. pylori, but not arsS-knockout (ΔarsS) or fleS-knockout (ΔfleS) H. pylori, showed a significant loss of viability upon exposure to NO compared with wild-type strain. Knockin crdS (ΔcrdS-in) significantly restored viability in the presence of NO. Global transcriptional profiling analysis of wild-type and ΔcrdS H. pylori in the presence or absence of NO showed that 101 genes were differentially expressed, including copper resistance determinant A (crdA), transport, binding and envelope proteins. The CrdR binding motifs were investigated by competitive electrophoretic mobility shift assay, which revealed that the two AC-rich regions in the crdA promoter region are required for binding. These results demonstrate that CrdR-crdA interaction enables H. pylori to survive under nitrosative stress.


Assuntos
Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Helicobacter pylori/metabolismo , Óxido Nítrico/metabolismo , Estresse Fisiológico , Sequência de Bases , Cobre/metabolismo , Proteínas de Ligação a DNA/metabolismo , Perfilação da Expressão Gênica , Técnicas de Inativação de Genes , Helicobacter pylori/genética , Dados de Sequência Molecular , Regiões Promotoras Genéticas
16.
Nucleic Acids Res ; 42(2): 739-47, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24153112

RESUMO

Non-B DNA structures are abundant in the genome and are often associated with critical biological processes, including gene regulation, chromosome rearrangement and genome stabilization. In particular, G-quadruplex (G4) may affect alternative splicing based on its ability to impede the activity of RNA polymerase II. However, the specific role of non-B DNA structures in splicing regulation still awaits investigation. Here, we provide a genome-wide and cross-species investigation of the associations between five non-B DNA structures and exon skipping. Our results indicate a statistically significant correlation of each examined non-B DNA structures with exon skipping in both human and mouse. We further show that the contributions of non-B DNA structures to exon skipping are influenced by the occurring region. These correlations and contributions are also significantly different in human and mouse. Finally, we detailed the effects of G4 by showing that occurring on the template strand and the length of G-run, which is highly related to the stability of a G4 structure, are significantly correlated with exon skipping activity. We thus show that, in addition to the well-known effects of RNA and protein structure, the relative positional arrangement of intronic non-B DNA structures may also impact exon skipping.


Assuntos
Processamento Alternativo , DNA/química , Éxons , Íntrons , Animais , Quadruplex G , Humanos , Camundongos , Especificidade da Espécie
17.
Nucleic Acids Res ; 41(13): 6371-80, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23658220

RESUMO

Transcription factor (TF) and microRNA (miRNA) are two crucial trans-regulatory factors that coordinately control gene expression. Understanding the impacts of these two factors on the rate of protein sequence evolution is of great importance in evolutionary biology. While many biological factors associated with evolutionary rate variations have been studied, evolutionary analysis of simultaneously accounting for TF and miRNA regulations across metazoans is still uninvestigated. Here, we provide a series of statistical analyses to assess the influences of TF and miRNA regulations on evolutionary rates across metazoans (human, mouse and fruit fly). Our results reveal that the negative correlations between trans-regulation and evolutionary rates hold well across metazoans, but the strength of TF regulation as a rate indicator becomes weak when the other confounding factors that may affect evolutionary rates are controlled. We show that miRNA regulation tends to be a more essential indicator of evolutionary rates than TF regulation, and the combination of TF and miRNA regulations has a significant dependent effect on protein evolutionary rates. We also show that trans-regulation (especially miRNA regulation) is much more important in human/mouse than in fruit fly in determining protein evolutionary rates, suggesting a considerable variation in rate determinants between vertebrates and invertebrates.


Assuntos
Evolução Molecular , Regulação da Expressão Gênica , MicroRNAs/metabolismo , Fatores de Transcrição/metabolismo , Animais , Sítios de Ligação , Drosophila melanogaster/genética , Humanos , Camundongos , Proteínas/genética
18.
BMC Genomics ; 13: 717, 2012 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-23256513

RESUMO

BACKGROUND: New genes that originate from non-coding DNA rather than being duplicated from parent genes are called de novo genes. Their short evolution time and lack of parent genes provide a chance to study the evolution of cis-regulatory elements in the initial stage of gene emergence. Although a few reports have discussed cis-regulatory elements in new genes, knowledge of the characteristics of these elements in de novo genes is lacking. Here, we conducted a comprehensive investigation to depict the emergence and establishment of cis-regulatory elements in de novo yeast genes. RESULTS: In a genome-wide investigation, we found that the number of transcription factor binding sites (TFBSs) in de novo genes of S. cerevisiae increased rapidly and quickly became comparable to the number of TFBSs in established genes. This phenomenon might have resulted from certain characteristics of de novo genes; namely, a relatively frequent gain of TFBSs, an unexpectedly high number of preexisting TFBSs, or lower selection pressure in the promoter regions of the de novo genes. Furthermore, we identified differences in the promoter architecture between de novo genes and duplicated new genes, suggesting that distinct regulatory strategies might be employed by genes of different origin. Finally, our functional analyses of the yeast de novo genes revealed that they might be related to reproduction. CONCLUSIONS: Our observations showed that de novo genes and duplicated new genes possess mutually distinct regulatory characteristics, implying that these two types of genes might have different roles in evolution.


Assuntos
Evolução Molecular , Duplicação Gênica , Genes Fúngicos/genética , Sequências Reguladoras de Ácido Nucleico/genética , Saccharomyces cerevisiae/genética , Sítios de Ligação , Nucleossomos/genética , Reprodução/genética , Saccharomyces cerevisiae/citologia , Saccharomyces cerevisiae/fisiologia , Seleção Genética , TATA Box/genética , Fatores de Transcrição/metabolismo
19.
Bioinformatics ; 28(5): 701-8, 2012 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-22238267

RESUMO

MOTIVATION: Gene regulation involves complicated mechanisms such as cooperativity between a set of transcription factors (TFs). Previous studies have used target genes shared by two TFs as a clue to infer TF-TF interactions. However, this task remains challenging because the target genes with low binding affinity are frequently omitted by experimental data, especially when a single strict threshold is employed. This article aims at improving the accuracy of inferring TF-TF interactions by incorporating motif discovery as a fundamental step when detecting overlapping targets of TFs based on ChIP-chip data. RESULTS: The proposed method, simTFBS, outperforms three naïve methods that adopt fixed thresholds when inferring TF-TF interactions based on ChIP-chip data. In addition, simTFBS is compared with two advanced methods and demonstrates its advantages in predicting TF-TF interactions. By comparing simTFBS with predictions based on the set of available annotated yeast TF binding motifs, we demonstrate that the good performance of simTFBS is indeed coming from the additional motifs found by the proposed procedures. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Redes Reguladoras de Genes , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Fatores de Transcrição/metabolismo , Imunoprecipitação da Cromatina , Regulação Fúngica da Expressão Gênica , Análise de Sequência com Séries de Oligonucleotídeos , Ligação Proteica , Proteínas de Saccharomyces cerevisiae/genética
20.
Artigo em Inglês | MEDLINE | ID: mdl-21844636

RESUMO

Metagenomics enables the study of unculturable microorganisms in different environments directly. Discriminating between the compositional differences of metagenomes is an important and challenging problem. Several distance functions have been proposed to estimate the differences based on functional profiles or taxonomic distributions; however, the strengths and limitations of such functions are still unclear. Initially, we analyzed three well-known distance functions and found very little difference between them in the clustering of samples. This motivated us to incorporate suitable normalizations and phylogenetic information into the functions so that we could cluster samples from both real and synthetic data sets. The results indicate significant improvement in sample clustering over that derived by rank-based normalization with phylogenetic information, regardless of whether the samples are from real or synthetic microbiomes. Furthermore, our findings suggest that considering suitable normalizations and phylogenetic information is essential when designing distance functions for estimating the differences between metagenomes. We conclude that incorporating rank-based normalization with phylogenetic information into the distance functions helps achieve reliable clustering results.


Assuntos
Análise por Conglomerados , Metagenoma/genética , Metagenômica/métodos , Filogenia , Bases de Dados Genéticas , Microbiologia Ambiental , Microbiota/genética , Modelos Genéticos
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