Filtering for Biological Relevance

Slides:



Advertisements
Similar presentations
Wilson WH et al. Proc ASH 2012;Abstract 686.
Advertisements

Mutations Section 12–4 This section describes and compares gene mutations and chromosomal mutations.
Unscrambling the genomic chaos of osteosarcomas reveals a recurrent gene fusion Leonardo A. Meza-Zepeda, PhD Department of Tumor Biology Institute for.
Gene set analyses of genomic datasets Andreas Schlicker Jelle ten Hoeve Lodewyk Wessels.
Application of Bioinformatics in Genetic Research Instructors: Dr. Henry Baker Dr. Luciano Brocchieri Dr. Michele Tennant Dr. Lei Zhou
CBioPortal Web resource for exploring, visualizing, and analyzing multidimentional cancer genomics data.
Promoter ABCDE 5’ 3’ 5’ ABCDE 3’5’ ACE AAAAA… 3’ 5’cap i. DNA ii. pre-mRNA iii. mRNA ACE iv. protein ABCDE i ii iii
End Show Slide 1 of 24 Copyright Pearson Prentice Hall 12-4 Mutations Outline 12–4: Mutations.
Slide 1 of 24 Copyright Pearson Prentice Hall Biology.
CCLE Cancer Cell Line Encyclopedia Alexey Erohskin.
CCRC Cancer Conference November 8, 2015.
NCRI Cancer Conference November 1, 2015.
K. Brennan, J.L. Koenig, A.J. Gentles, J.B. Sunwoo, O. Gevaert
Canadian Bioinformatics Workshops
Comparison between Pathologic Characteristics of Her2 Negative and Positive Breast Cancer in a Single Cancer Center in Jordan DR Majdi A. Al Soudi, MD,
Variation among organisms
Volume 19, Issue 5, Pages (May 2017)
Gapless genome assembly of Colletotrichum higginsianum reveals chromosome structure and association of transposable elements with secondary metabolite.
::: Schedule. Biological (Functional) Databases
Determination of Molecular Subtypes of Diffuse Large B-Cell Lymphoma Using a Reverse Transcriptase Multiplex Ligation-Dependent Probe Amplification Classifier 
FREQUENCIES of altered genes RECURRENT variants & mutated genes
Figure 1. Exploring and comparing context-dependent mutational profiles in various cancer types. (A) Mutational profiles of pan-cancer somatic mutations,
Volume 44, Issue 1, Pages (January 2016)
Volume 18, Issue 13, Pages (March 2017)
Strategy Description Discovery Validation Application
The Functional Impact of Alternative Splicing in Cancer
Targeted Next-Generation Sequencing of Cancer Genes in Advanced Stage Malignant Pleural Mesothelioma: A Retrospective Study  Marco Lo Iacono, PhD, Valentina.
A bioinformatic analysis of microRNAs role in osteoarthritis
Nat. Rev. Clin. Oncol. doi: /nrclinonc
A Long Noncoding RNA Signature That Predicts Pathological Complete Remission Rate Sensitively in Neoadjuvant Treatment of Breast Cancer  Gen Wang, Xiaosong.
Sequence Based Analysis Tutorial
Identification of Somatic Mutations in Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type by Massive Parallel Sequencing  Sylvain Mareschal, Anne.
Volume 133, Issue 5, Pages (November 2007)
Volume 72, Issue 4, Pages (October 2017)
A: OAZ1 mRNA transcript of 775-1, and parental cell lines showing the stop codon introduced by the nonsense mutations in the and transcripts,
Volume 9, Issue 3, Pages (September 2017)
Volume 23, Issue 4, Pages (April 2018)
Transcriptional Landscape of Cardiomyocyte Maturation
Recurrence-Associated Long Non-coding RNA Signature for Determining the Risk of Recurrence in Patients with Colon Cancer  Meng Zhou, Long Hu, Zicheng.
The Functional Impact of Alternative Splicing in Cancer
Volume 4, Issue 3, Pages (August 2013)
Enriched gene functions responding to irradiance and pO2.
Closing Cancer Cases Not Under Active Care
Signature of CRC‐associated gut microbial species Relative abundances of 22 gut microbial species, collectively associated with CRC, are displayed as heatmap.
Volume 24, Issue 4, Pages (July 2018)
Parallel evolution of coding sequences above neutral expectation.
Figure S1: An overview of the variants in signalling pathways and molecular processes known to be affected in SMZL, which were identified by whole exome.
Systems-wide Identification of cis-Regulatory Elements in Proteins
Wei Jiang, Yuting Liu, Rui Liu, Kun Zhang, Yi Zhang  Cell Reports 
Identification of the Transcriptional Targets of FOXP2, a Gene Linked to Speech and Language, in Developing Human Brain  Elizabeth Spiteri, Genevieve.
Deletion of Crebbp in the GC cooperates with BCL2 deregulation to promote lymphomagenesis. Deletion of Crebbp in the GC cooperates with BCL2 deregulation.
Varying Intolerance of Gene Pathways to Mutational Classes Explain Genetic Convergence across Neuropsychiatric Disorders  Shahar Shohat, Eyal Ben-David,
Volume 19, Issue 5, Pages (May 2017)
Landscape of genomic alterations in 444 tumors from 429 patients with mCRPC. Landscape of genomic alterations in 444 tumors from 429 patients with mCRPC.
Cancer Cell Line Encyclopedia
The Ultraviolet Fingerprint Dominates the Mutational Spectrum of the p53 and Ha-ras Genes in Psoralen + Ultraviolet A Keratoses from Psoriasis Patients 
Volume 15, Issue 2, Pages (April 2016)
Figure 1. Identification of three tumour molecular subtypes in CIT and TCGA cohorts. We used CIT multi-omics data ( Figure 1. Identification of.
Practical Bioinformatic DNA-Sequencing Pipeline for Detecting Oncogene Amplification and EGFRvIII Mutational Status in Clinical Glioblastoma Samples 
Volume 2, Issue 3, Pages (March 2016)
Enrichment of KEGG pathways in microbial genes in different samples.
Distinct molecular and clinical correlates of H3F3A mutation subgroups
Copyright Pearson Prentice Hall
by Pierre Sesques, and Nathalie A. Johnson
Relationship of PMBL to Hodgkin lymphoma.
CREBBP loss-of-function results in gene expression repression signature. CREBBP loss-of-function results in gene expression repression signature. A–D,
Gene expression signature that predicts early molecular response failure in chronic-phase CML patients on frontline imatinib by Chung H. Kok, David T.
Concordance between the genomic landscape identified by whole-exome sequencing of plasma cfDNA and tumor; DNA and recurrence of KDR/VEGFR2 oncogenic mutations.
Comparison of the van gene clusters.
DO NOT POST #4054 Gene expression Difference (GED) Revealed Immune Function Gene UP- or Down-regulation as Tumor-associated Inflammatory Cell (TAIC) Infiltration.
Presentation transcript:

Filtering for Biological Relevance S_Figure 1 String-Analysis depicting BCL2-association of genes mutated in t(14;18)-negative FL at low confidence. See also gene lists in S_Table 6b, S_Table 8 and Table 2 as well as BCL2-association results given in Table 3a-c, S_Table 11a-d and S_Table 12a+b. Selectively mutated in t(14;18)-negative FL recurrently and more frequently mutated in t(14;18)-negative FL n= 1.435 n= 88, without pipeline bias n= 23 BCL2 BCL2 BCL2 Filtering for Biological Relevance (e.g. bioinformatics predictors, literature) Validation by Sanger Sequencing

S_Figure 2 Heatmap with t(14;18)-negative and t(14;18)-positive FL depicting mutations in IGV-genes within the WES dataset. None of the mutations affecting a t(14;18)-negative FL led to an amino acid (AA)-exchange that resulted in an asparagin while ~21% of the mutations in t(14;18)-positive FL revealed an asparagin (see also Table 4). ?>?: exchange to any AA; ?>N: exchange to an asparagin. The occurence of mutations is highlighted in yellow. Exchanges to asparagin are highlighted in green. 1x: the exchange to asparagin was detected only for one of the detected mutations in the respective gene.

included in the KEGG-NFkB-pathway. SNVs were significantly enriched S_Figure 3 Comparison of the SNV-profile of FL with and without t(14;18) with regard to genes included in the KEGG-NFkB-pathway. SNVs were significantly enriched in t(14;18)-negative FL by a p-value of 0.01 or lower according to Fisher‘s exact test. p<0.01

S_Table 15 Comparison of the SNV-profiles of FL with and without t(14;18) with regard to genes differentially mutated between ABC and GCB DLBCL according to a previous publication. 56 Values are given in percent and are rounded up and down according to mathematical guidelines. Gene Signature ABC GCB PMBL T_NEG T_POS MYD88 28 10 23 4 cd79b 25 2 PIM1 33 8 11 CREBBP 6 31 38 61 EZH2 18 15 14 TNFRSF14 17 BCL2 1 24 46

S_Table 1 Clincal information as well as BCL2-breakpoint and BCL2-protein status of11 FL cases (10 t(14;18)-negative and 1 t(14;18)-positive) that were retrieved from the files of the Institute of Pathology in Würzburg. These cases were applied to whole exome sequencing.   Grade DOB BCL2_BAP BCL2_IHC_DAKO BCL2_IHC_E17 BCL2_IHC_final Note Clinical Stage FL_6 2 03.12.1955 neg neg/weak weak/positive pos n/a FL_7 1-2 10.05.1942 II A FL_10 26.03.1934 FL_2 3a 23.11.1922 FL_3 07.04.1928 FL_9 12.11.1960 I A FL_11 17.01.1958 FL_8 3A 28.03.1924 II-III A, staging not complete FL_4 09.10.1938 FL_5 26.01.1938 negative Relapse Initial III A, Relapse: IIIa FL_1 19.06.1928 weak/neg Initial III B, Relapse: II A