GeneAnnot: comprehensive two-way linking between oligonucleotide array probesets and GeneCards genes

Chalifa‐Caspi, Vered; Yanai, Itai; Ophir, Ron; Rosen, Naomi; Shmoish, Michael; Benjamin-Rodrig, Hila; Shklar, Maxim; Stein, Tsippi Iny; Shmueli, Orit; Safran, Marilyn; Lancet, Doron

doi:10.1093/bioinformatics/bth081

Cited by 55 publications

(53 citation statements)

References 5 publications

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“…Human Ikaros gene (NM_006060) was used as query sequences for the BLAST programs. The expression profiles for normal human tissues were obtained from GeneAnnot (36) and ArrayExpress (37). Northern analysis of NCBI's uniGene dataset was also extracted (34,35).…”

Section: In Silico Expression Analyses Of Human Ikaros Genementioning

confidence: 99%

Integrative genomic analyses on Ikaros and its expression related to solid cancer prognosis

Yang

Luo²,

Wei³

2010

Oncol Rep

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Abstract. Ikaros is a member of the Kruppel family of zinc finger DNA-binding proteins. The Ikaros protein contains two separate regions of zinc-finger domains: 4 DNA-binding zinc fingers near the N-terminus and 2 zinc fingers for proteinprotein interactions near the C-terminus. Here, we identified the Ikaros gene from 14 vertebrate genomes and found Ikaros existed in all kinds of vertebrate including fish, amphibians, birds and mammals. Moreover, except rat and Xenopus tropicalis Ikaros proteins, which lack the first C2H2-type 1 Zinc finger region, all identified Ikaros proteins contain six C2H2-type 1 Zinc finger regions. We found human Ikaros gene showed a predominant expression in the liver, lymph node, thymus, intestine, lung, mammary gland, bone marrow, brain, heart, placenta and prostate. Moreover, four available SNPs disrupted an existing exonic splicing enhancer were identified in Ikaros. Besides the reported acute lymphoblastic leukemia (ALL), the expression of Ikaros was related to the prognosis of 13 cases of cancers including blood cancers, breast, lung, ovarian and skin cancer. Moreover, the relationship between the expression of Ikaros and prognosis varied in different cancers, even in the same cancer from different database. Two tumor-related transcriptional factor (c-Fos and Elk-1) binding sites were identified within the 1.5-kb regions upstream of the transcriptional start site of human Ikaros, which may be involved in the effect of Ikaros in tumors. IntroductionThe Ikaros (IKZF1, Lyf-1) is a member of the Kruppel family of zinc finger DNA-binding proteins 1 (1). The Ikaros protein contains two separate regions of zinc-finger domains: 4 DNA-binding zinc fingers near the N-terminus and 2 zinc fingers for protein-protein interactions near the C-terminus. The human Ikaros gene, located at 7p12, contains seven exons and gives rise to at least eight isoforms by alternative splicing (2). All isoforms share a common C-terminal domain that contains a transcriptional activation domain and two zinc finger motifs required for hetero-or homodimerization and for interactions with other proteins, but these isoforms differ in the number of N-terminal zinc finger motifs. Long isoforms (Ik1 to 3) have at least three zinc fingers which are capable of binding DNA and considered to be functional. Short isoforms (Ik4 to 8) lack two or more zinc-finger domains, so they cannot bind DNA and impair the function of Ikaros proteins in a dominant-negative manner (3-6).Ikaros is a transcription factor, which plays an important role in controlling hematopoietic, particularly lymphoid cell differentiation, proliferation and function by binding upstream regulatory regions of target genes and aiding in their recruitment to pericentromeric heterochromatin (PC-HC) (7). This process leads to either activation or repression of transcription of these target genes by elaborate splicing regulation of Ikaros transcripts (3-6). Accordingly, abnormalities in splicing regulation of Ikaros would lead to significant pathological manifestat...

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Section: In Silico Expression Analyses Of Human Ikaros Genementioning

confidence: 99%

Integrative genomic analyses on Ikaros and its expression related to solid cancer prognosis

Yang

Luo²,

Wei³

2010

Oncol Rep

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“…All arrays adhered to author-recommended quality control thresholds, including GAPDH and ␤-actin 3Ј/5Ј-probeset ratios, array scaling factors, mean array intensity distributions, and positive/negative edge elements. Probesets were annotated using version 24 of the Affymetrix probeset annotation file (see Supplemental Table 1 for probeset annotations used), with some manual annotation using GeneAnnot (8). 1 RNA interference transfection and proliferation/migration assays.…”

Section: Cell Culture and Isolation Cd4mentioning

confidence: 99%

Longitudinal system-based analysis of transcriptional responses to type I interferons

Pappas

Coppola

Gabatto

et al. 2009

Physiological Genomics

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Type I interferons (IFNs) are pleiotropic cytokines that modulate both innate and adaptive immune responses. They have been used to treat autoimmune disorders, cancers, and viral infection and have been demonstrated to elicit differential responses within cells, despite sharing a single receptor. The molecular basis for such differential responses has remained elusive. To identify the mechanisms underlying differential type I IFN signaling, we used whole genome microarrays to measure longitudinal transcriptional events within human CD4 ϩ T cells treated with IFN-␣2b or IFN-␤1a. We identified differentially regulated genes, analyzed them for the enrichment of known promoter elements and pathways, and constructed a network module based on weighted gene coexpression network analysis (WGCNA). WGCNA uses advanced statistical measures to find interconnected modules of correlated genes. Overall, differential responses to IFN in CD4 ϩ T cells related to three dominant themes: migration, antigen presentation, and the cytotoxic response. For migration, WGCNA identified subtypespecific regulation of pre-mRNA processing factor 4 homolog B and eukaryotic translation initiation factor 4A2, which work at various levels within the cell to affect the expression of the chemokine CCL5. WGCNA also identified sterile ␣-motif domain-containing 9-like (SAMD9L) as critical in subtype-independent effects of IFN treatment. RNA interference of SAMD9L expression enhanced the migratory phenotype of activated T cells treated with IFN-␤ compared with controls. Through the analysis of the dynamic transcriptional events after differential IFN treatment, we were able to identify specific signatures and to uncover novel genes that may underpin the type I IFN response.human; T cell; cytokines; gene regulation INTERFERONS (IFNs) are pleiotropic molecules implicated in a wide range of cellular responses (44) and are Federal Drug Administration-approved therapeutics for the treatment of cancer, infection, and autoimmunity (49). Based on sequence homology and structure, IFNs are divided into three classes: types I, II, and III. Type I IFNs include IFN-␣ (15 known ␣-subtypes), IFN-␤, and IFN-, whereas type II IFN consists only of IFN-␥ and type III IFN consists only of IFN-. All type I IFNs activate a common cell surface receptor [the IFN receptor (IFNR)], which exists as two separate polypeptides (IFNAR1 and IFNAR2) with no intrinsic dimerization capacity (12). Binding of type I IFNs to IFNAR2, recruitment of IFNAR1, and stabilization of a heterotrimeric ligand/receptor complex activate members of the Jak1/tyrosine kinase 2 (Tyk2) and JAK/STAT pathways (12, 45). Phosphorylated STAT1/ STAT2 heterodimers form transcriptional activation complexes with IFN regulatory factor (IRF)9/p48, translocate to the nucleus, and drive the expression of numerous genes, including myxovirus resistance protein 1 (MX1), 2Ј,5Ј-oligoadenylate synthetase 1, and double-stranded RNA-activated protein kinase (EIF2AK2).Although type I IFNs share the same cognate receptor and und...

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“…25 This difference using different methodologies for quantification of expression may be due to the following reasons: KIR mRNA sequences are highly similar, and DNA microarray probe sets are not as specific as RNA-seq for the measurement of the expression of individual KIR genes. Based on the GeneAnnot database, 26 most of the Affymetrix probe sets for KIR genes have many nonspecific targets, which can potentially influence the quantification of mRNA levels. Therefore, RNA-seq reads may have more unique coverage of the transcripts for regions that are different from other family members.…”

Section: Discussionmentioning

confidence: 99%

Diagnostic and Biological Significance of KIR Expression Profile Determined by RNA-Seq in Natural Killer/T-Cell Lymphoma

Küçük

Gong

et al. 2016

The American Journal of Pathology

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Natural killer/T-cell lymphoma (NKTCL) is a rare, aggressive form of non-Hodgkin lymphoma that is generally incurable at more advanced stages with systemic involvement. Clonal diagnostic markers (eg, unique T-or B-cell receptor rearrangements) are not available for NKTCLs. Killer cell immunoglobulin like receptors (KIRs) are a family of type I transmembrane glycoproteins involved in the inhibition or activation of NK cells. A restricted expression profile of KIRs has been proposed as clonal markers of NK-cell proliferations. Here we evaluated the transcription profile of all KIR family genes and C-type lectin receptor genes using RNA sequencing on NKTCL cases (n Z 17) and NK-cell lines (n Z 3). The expression of all KIRs tended to be markedly reduced or absent in NKTCL, except for the KIR family member killer Ig-like receptor 2DL4 (KIR2DL4; alias CD158D), which was selectively overexpressed in the majority (59%) of cases. No specific expression pattern was observed for C-type lectin receptors. KIR2DL4 is an unusual member of the KIR family that recognizes human leukocyte antigen G and mediates NK-cell activation through inducing proliferation and survival pathways such as AKT and NF-kB. Stable knockdown of KIR2DL4 in two malignant NK-cell lines with high KIR2DL4 expression significantly reduced cell growth. Selective overexpression of KIR2DL4 and downregulation of inhibitory KIRs may contribute to NKTCL pathogenesis. (Am J Pathol 2016, 186: 1435e1441; http://dx

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GeneAnnot: comprehensive two-way linking between oligonucleotide array probesets and GeneCards genes

Abstract: Program description and statistics http://genecards.weizmann.ac.il/geneannot/DOC/index.html

Cited by 55 publications

References 5 publications

Integrative genomic analyses on Ikaros and its expression related to solid cancer prognosis

Integrative genomic analyses on Ikaros and its expression related to solid cancer prognosis

Longitudinal system-based analysis of transcriptional responses to type I interferons

Diagnostic and Biological Significance of KIR Expression Profile Determined by RNA-Seq in Natural Killer/T-Cell Lymphoma

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