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Summary The following table summarizes data sets that have completed analysis by the ALEXA-Seq approach. Additional details for these projects are provided below. Additional projects that are in the process of being analyzed are also listed. Further additional projects are being analyzed externally at others centres, such as the LBL Life Sciences Division who are currently mirroring this site and using ALEXA-Seq to analyze some of their data: alexa-seq-lbl.org. The Genome Institute of the Washington University School of Medicine is also using ALEXA-seq: alexa-seq.genome.wustl.edu The ALEXA-Seq method is actively being updated to include more analyses and to help the user efficiently identify interesting alternative expression events. Currently, updates are being added to the 'Breast' project first. Try that one to see all the latest additions.
Results The following sections link to summaries of alternative expression results for datasets analyzed by the ALEXA-Seq approach.
View a summary of alternative expression results or search for a specific gene by clicking the 'Summary' or 'Search' buttons below. Throughout the data viewer, use the following buttons to
activate or hide content: (1) 5-FU resistance in colorectal cancer cell lines (Human)
Experimental description: Comparison of fluorouracil (5-FU) sensitive and resistant colorectal cancer cell lines. 5-FU is a pyrimidine analog belonging to the family of drugs called antimetabolites and is typically administered as part of a cocktail often containing leucovorin, oxaliplatin or irinotecan. 5-FU resistant colorectal cancer cells were derived by exposure to increasing concentrations of 5-FU. The resistant derivative was then compared to the original (sensitve) cell line. Resistant derivatives had at least 10-fold greater IC50 for 5-FU. See Griffith et al. for further details. Basic Statistics Project ID: '5FU' Number of Libraries (i.e. samples, tissues, treatments): 2 Paired read count: 262,923,040 Supplementary Data All supplementary data files for Griffith et al. are available from out public FTP repository: FTP Raw data Fastq data files: MIP101 (5-FU sensitive) | MIP/5FU (5-FU resistant) Analysis files Expression values for all feature types: MIP101 (5-FU sensitive) | MIP/5FU (5-FU resistant) Differential Expression values for all feature types: MIP101 versus MIP/5FU (5-FU resistant minus 5-FU sensitive) Splicing index values for all feature types: MIP101 versus MIP/5FU (5-FU resistant minus 5-FU sensitive) Pathway analysis: Significant functional categories Validation experiments Primer sequences, Gels images, Sanger sequences, qPCR data, etc. for validation experiments described in the manuscript: ValidationResultsPackage.zip Examples: H19 - Under-expressed in 5-FU resistant cells relative to sensitive KRT20 - Over-expressed in 5-FU resistant cells relative to sensitive OLR1 and c12orf59 - Virtually complete loss of expression in resistant cells. These two genes are adjacent and arranged in a head-to-head fashion UMPS - Reciprocal differential expression of two isoforms, involving either inclusion or skipping of exon 2 OCIAD1 - Over-expression of several novel exon-skipping isoforms, all involving the donor site of exon 4 LAMA3 - Reciprocal differential expression of a short and long isoform C12orf63 - Over-expression of a novel transcript of this locus, consisting of exon 18 to 27 EPB41L3 - Over-expression of a novel transcript of this locus, consisting of exon 15 to 24 KIAA0391 - Over-expression of one known transcript. Expression of a second known isoform is unchanged SLC24A1 - Over-expression of one known transcript. Expression of a two additional known isoforms is unchanged ATP8A1 - Inclusion of a cryptic exon (within intron 7) that is not currently annotated by EnsEMBL IQGAP3 - Over-expression of an intron 10 retaining isoform (2) Treatment response in Neuroblastoma tumours (Human)
Experimental description: Tumour initiating cells (TICs) were isolated from a Neuroblastoma tumour of a patient that had received first line chemotherapy. Additional TICs were subsequently isolated from the same patient approximately 2 years later after secondary treatments. RNA was isolated from each population of TICs and used for RNA sequencing to examine the evolution of Neuroblastoma (Manuscript in preparation). Basic Statistics Project ID: 'Neuroblastoma' Number of Libraries (i.e. samples, tissues, treatments): 2 Paired read count: 115,665,612 Supplementary Data Release of raw data is pending publication... Examples: APP - Descrease in abundance of Alzheimer disease amyloid protein TJP1 - Increase in abundance of Tight junction protein ZO-1 RGS2 - Increase in abundance of Regulator of G-protein signaling 2 PARL - Increase in abundance exon 8 skipping isoform of Presenilins-associated rhomboid-like protein PARP11 - Increase in abundance exon 3 skipping isoform of poly-A polymerase 11 TRAK1 - Retention of introns 8-11 in post-treatment tumour TCF4 - Possible alternative transcript initiation resulting in increased abundance of a novel exon 3 to exon 10 containing isoform (3) Mouse organogenesis (MORGEN) - Liver, Heart, Artery, etc. (Mouse)
Experimental description: Liver tissues were isolated from day 14.5 mouse embryos and adult mice. Heart tissues were isolated from day 11.5 and 12.5 mice. Aorta and artery tissues were isolated from developing mice. RNA was isolated from each tissue type and RNA sequencing was performed to examine the development of mouse tissues (Manuscript in preparation). Basic Statistics Project ID: 'Morgen' Number of Libraries (i.e. samples, tissues, treatments): 6+ Paired read count: 1,195,755,933 Supplementary Data Release of raw data is pending publication... Examples: H19, IGF2 & IGF2R - Known imprinted genes, all highly expressed in embryo and silenced in adult liver Fam171a1 - Reciprocal differential expression of known alternative isoforms Epb4.1l5 - Exon 18 to 26 are alternatively expressed, indicating a possible embryo specific isoform (corresponds to a known alternatve transcript produced by alternative poly-adenylation) Foxn2 - A novel exon skipping isoform involving skipping of exon 5 is specific to adult liver Zfp187 - A novel exon skipping isoform involving skipping of exons 3 & 4 is largely specific to embryonic liver (overall gene expression is not changed) Ugcgl1 - Shift in expression from exon 21 containing to exon 21 skipping isforms between embryonic and adult liver Arap1 - Complicated shift in splicing path between embyronic and adult liver (4) Sutent response in ovarian cancer xenografts (Human tumours in mice)
Experimental description: Human ovarian cancer xenografts were established in mice. Mice were then treated with the drug Sutent (Sunitinib) an oral, small molecule, multi-targeted receptor tyrosine kinase inhibitor. Xenografts were isolated from treated and control mice and RNA was isolated from these tumours for comparison. The first treatment represents a 24-hour treatment. Additional time points represented by xenograft passages (1-2 weeks between each) are forthcoming (Manuscript in preparation). Basic Statistics Project ID: 'Sutent' Number of Libraries (i.e. samples, tissues, treatments): 2 Paired read count: 30,291,765 Supplementary Data Release of raw data is pending publication... Examples: Very little change in expression between control and 24-hour treatment samples (5-7) Iressa response in skin, lung and breast cancer cell lines (Human)
Experimental description: Human skin lung and breast cancer cell lines were grouped into Iressa sensitive and insensitive according to Iressa IC50. The transcriptomes of each of these cell lines were profiled before and after treatment with Iressa or a combination of Iressa+Tretinoin (Manuscript in preparation). Basic Statistics Project IDs: 'IRS', 'IRI', and 'IRTR' Number of Libraries (i.e. samples, tissues, treatments): 14 Paired read count: 174,404,866 Supplementary Data Release of raw data is pending publication... Iressa-treated Iressa-Sensitive tumours ('IRS')
Examples: EGR1 - Expression is reduced by Iressa exposure in all three cell lines. FOSL1 - Expression is reduced by Iressa exposure in all three cell lines. TGM2 - Expression is reduced by Iressa exposure in all three cell lines. Iressa-treated Iressa-Insensitive tumours ('IRI')
Examples: Very little change in expression is observed in response to Iressa treatment Iressa/Tretinoin-treated Iressa-Insensitive tumours ('IRTR')
Examples: CYP26A1 - Expression is increased in response to combined treatment (CYP26A1 is a retinoic acid-metabolizing cytochrome). CDH5 - Expression is increased in response to combined treatment. (8) Tumor Evolution in Multiple Myeloma (Human)
Experimental description: Whole transcriptome shotgun sequencing was applied to bone marrow samples taken pre-treatment and at tumour relapse from a multiple myeloma patient to evaluate changes in the tumour composition during its evolution. Samples were further separated into an unpurified and tumour enriched fraction (by CD138+ selection) to guage the efficacy of immunomagnetic selection of plasma cells and the ability to observed expression changes in unpurified bone marrow. Sample names are abreviated as follows: PreTx_Un (Pre-Treatment, Unenriched), PostTx_Un (Post-Treatment, Unenriched), PreTx_En (Pre-Treatment, Enriched), PostTx_Un (Post-Treatment, Enriched) Basic Statistics Project ID: 'MultipleMyeloma' Number of Libraries (i.e. samples, tissues, treatments): 4 Paired read count: 346,824,962 Supplementary Data Release of raw data is pending publication... Examples: CHAC1 - Gene with increased abundance Post-Treatment ELA2 - Cell enrichment is associated with reduced abundance of many genes, including this one CASP4 - A novel exon-skipping isoform (exons 6,7,8 skipped) is expressed) Post-Treatment but not Pre-Treatment Work in progress... (9) Diffuse large B-cell lymphoma versus a pooled B-cell background (Human)
Experimental description: Comparative analysis of a single Diffuse Large B-Cell Lymphoma patient transcriptome against a pool of normal B-Cells isolated from the tonsils of four individuals. The first 'Summary' button takes you to results for the DLBCL compared to a pooled library (project: 'Lymphoma'). The second 'Summary' button corresponds to the same comparison but also contains values for each individual B-cell library used to create the pooled library (project: 'Lymphoma2'). Basic Statistics Project ID: 'Lymphoma' Number of Libraries (i.e. samples, tissues, treatments): 5 Paired read count: 471,405,196 Supplementary Data Release of raw data is pending publication... Examples: TBC1D4 - Alternative isoform expression in DLBCL compared to normal B-Cells BRE - Alternative first exon usage in DLBCL compared to normal B-Cells RTKN2 - Alternative isoform expression in DLBCL compared to normal B-Cells PTS - Increased expression of exon 3 skipping isoform in DLBCL CD40 - Loss of expression of one of four known CD40 isoforms (containing an 'E4b_E5c' junction) (10) Androgen sensitivity in prostate cancer cell lines (Human)
Experimental description: Comparison of prostate cancer cell lines derived from the well studies LnCAP cell line One cell line is 'C42' and the second was treated with an Androgen Receptor (AR) KnockIn Basic Statistics Project ID: 'LnCAP_AR_KnockIn' Number of Libraries (i.e. samples, tissues, treatments): 2 Paired read count: 170,502,176 Supplementary Data Expression, differential expression and alternative expression values for all feature types: LnCAP_AR_KnockIn_ResultFiles.tar.gz Release of raw data is pending publication... Examples: AR - The 6th most highly over-expressed gene in the AR knock-in cells. In the knock-in line, AR is expressed at rank #21 overall ETV1 - The most highly over-expressed gene in the AR knock-in cells KIF4A - Exon 29 containing isoform is increased in AR knock-in cells, exon 29 skipping isoform is decreased SLC38A2 - C42 cells express an exon 16 skipping isoform (i.e. E15a_E17a) that is lost in the AR knock-in line DBN1 - A novel exon 7 skipping isoform (i.e. E6a_E8a) is gained in AR knock-in cells TMEM106C - A novel isoform skipping exons 3-7 (i.e. E2a_E8a) is over-expressed in AR knock-in cells UBE3C - An exon 22 skipping isoform (i.e. E21a_E23a) is lost in AR knock-in cells NUP93 - Alternative transcript initiation. An isoform containing an active intronic region (I3_AR3) corresponding to an alternative first exon is over-expressed in AR knock-in cells UPRT - Cryptic exon or alternative first exon within intron 1 (i.e. I1_AR1) is increased in AR knock-in cells C11orf75 - Novel exon within intron 1 (i.e. I1_AR1) is over-expressed in AR knock-in cells (11) Follicular lymphoma (FL) transformation to diffuse large B-cell lymphoma (DLBCL) (Human)
Experimental description: Comparison of follicular lymphoma (FL) to a transformed diffuse large b-cell lymphoma (DLBCL) arising in the same patient Basic Statistics Project ID: 'FL_Trans' Number of Libraries (i.e. samples, tissues, treatments): 2 Paired read count: 161,439,548 Supplementary Data Release of raw data is pending publication... Examples: Work in progress (12) Follicular lymphoma (FL) treatment response (Human)
Experimental description: Comparison of follicular lymphoma (FL) samples obtained before and after treatment with an R-CHOP chemotherapy regime Basic Statistics Project ID: 'FL_Tx' Number of Libraries (i.e. samples, tissues, treatments): 2 Paired read count: 111,190,555 Supplementary Data Release of raw data is pending publication... Examples: Work in progress (13) Normal breast tissue types. Luminal versus myoepithelial (Human)
Experimental description: Comparison of normal breast tissues that were resected and then sorted to enrich for luminal epithelial (CD227+), myoepithelial (CD10+), and stem-like (CD73+) cell populations derived from a single individual. Recently, we added comparisons to vHMECs (variant human mammary epithelial cells) a partially transformed breast cancer cell line also derived from the same individual. Finally an unrelated hESC library was added (HS1272). Summary of libraries
Luminal epithelial breast cells (CD227+ aka MUC1) - 'Lum_Epi' (HS1187) and 'Lum_Epi2' (A01029) Basic Statistics Project ID: 'Breast' Number of Libraries (i.e. samples, tissues, treatments): 4 Paired read count: 629,786,546 Supplementary Data Release of raw data is pending publication... Examples: CD10 (MME) - Used to sort myoepithelial cells. Ranked #2 among DE genes. 422-fold higher in myoepithelial than luminal CD227 (MUC1) - Used to sort luminal cells. Ranked #171 among DE genes. 26-fold higer in luminal cells than myoepithelial COL17A1 - Ranked #1 among DE genes over-expressed in myoepithelial breast cells ANKRD30A - Ranked #1 among DE genes over-expressed in luminal breast cells FRMD4A - Differential transcript inititation site usage between Myoepithelial and Luminal cells FRMD4B - Differential transcript inititation site usage between Myoepithelial and Luminal cells PIK3R1 - Differential transcript inititation site usage between Myoepithelial and Luminal cells INPP4B - Differential transcript inititation site usage between Myoepithelial and Luminal cells DMKN - Differential transcript inititation site usage between Myoepithelial and Luminal cells PALLD - Differential transcript inititation site usage between Myoepithelial and Luminal cells LAMA3 - Differential transcript inititation site usage between Myoepithelial and Luminal cells LIMA1 - Differential transcript inititation site usage between Myoepithelial and Luminal cells DST - Differential transcript inititation site usage between Myoepithelial and Luminal cells CA12 - Alternative expression of two known isoforms (exon 9 skipped versus included) CLSTN1 - Alternative expression of two known isoforms (exon 11 skipped versus included) ERBB2IP - Alternative expression of two known isoforms (exon 22-23 skipped versus included) ELMO3 - Alternative expression of a novel isoform (exon 15-16 skipped versus included) EFEMP1 - Gain of novel exon 7 and exon 7-8 skipping isoforms in myoepithelial cells (14) Oligodendroglioma (A survey of primary bulk tumours and tumour initiating cells) (Human)
Experimental description: Comparison of five primary oligodenrogliomas to a single tumour initiating cell population derived from one of the primary tumours Basic Statistics Project ID: 'Oligo' Number of Libraries (i.e. samples, tissues, treatments): 6 Paired read count: 752,967,939 Supplementary Data Release of raw data is pending publication... Examples: Work in progress (15) Neuroblastoma evolution (Normal neural crest cells, primary tumour, metastasis, remission and relapse) (Human)
Experimental description: Comparison of various Neuroblastoma related libraries, including primary tumours, tumour initiating cells (TICs), normal neural crest cells (SKPs), and and subsets of these groups that exhibit MYCN amplification versus normal MYCN copy number. Basic Statistics Project ID: 'NeuroEvolution' Number of Libraries (i.e. samples, tissues, treatments): 23 Paired read count: 2,071,105,180 Supplementary Data Release of raw data is pending publication... Examples: Work in progress (16) Allen Brain Atlas - Frontal lobe versus amgdala - Pilot project (Human)
Experimental description: Comparison of human frontal lobe and amygdala tissues from a single individual. RNA from each of these tissues was prepared for RNA sequencing using three different approaches: (1) 'mRNA-seq' - standard library construction using polyA+ RNA, (2) library construction using riboMinus reduction, (3) library construction using amplified RNA. Basic Statistics Project ID: 'AllenBrain' Number of Libraries (i.e. samples, tissues, treatments): 6 Paired read count: 415,662,977 Supplementary Data Release of raw data is pending publication... Examples: Work in progress (17) The genetics of disease progression in myelodysplastic syndrome (MDS) (Human)
Experimental description: MDS libraries representing multiple timepoints in the progression of MDS during diagnosis and treatment. Early stage MDS, loss of response to lenalidomide treatment, transformation to acute myeloid leukemia. Basic Statistics Project ID: 'MDS' Number of Libraries (i.e. samples, tissues, treatments): 3 Paired read count: 129,349,959 Supplementary Data Release of raw data is pending publication... Examples: Results for this project are not publicly available. (18) Comparison of DLBCL subtypes (of ABC versus GCB cell origin) (Human)
Experimental description: Comparison of two groups of diffuse large B-cell lymphomas derived from ABC and GCB cells respectively. Basic Statistics Project ID: 'DLBCL_ABC_GCB' Number of Libraries (i.e. samples, tissues, treatments): 3 Paired read count: 3,233,495,655 Supplementary Data Release of raw data is pending publication... Examples: Work in progress. More data sets Collaborations that would benefit from ALEXA-Seq analysis are added as they are identified. Feel free to contact us for more details: Contact Us Help with visualizations Note that the ALEXA-Seq viewer pages linked above make use of scalable vector graphics (SVGs). You may need to update your browser or install an SVG viewer to view the figures. SVG images can be converted to alternate formats or viewed with specialized software to assist in the creation of figures. More information on these topics can be found here: Detailed Instructions About the ALEXA-Seq data viewer The following is a list of utilities and resources used to create the ALEXA-Seq visualization tool: Figures and statistics: The R Project and Bioconductor Scalable Vector Graphics was chosen as the image format: XML Graphics for the Web General web programming: Perl Database management systems: MySQL and Berkeley DB Web animation java-script used to give the viewer a 'Web 2.0' style: Google AJAX APIs and Dynamic Drive Indexing and search functionality: The Xapian Project and Omega Web traffic analysis: Google Analytics |
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