Genomic approaches towards finding cis -regulatory modules (CRM) in - PowerPoint PPT Presentation

Genomic approaches towards finding cis -regulatory modules (CRM) in animals Matthew I. Omoruyi 21.01.2013 www.helsinki.fi/yliopisto 1.11.2018 1

Introduction CRM is a stretch of DNA, usually 100 – 1000 DNA base pairs in length, where a number of transcription factors can bind and regulate expression of nearby genes www.helsinki.fi/yliopisto 1.11.2018 2

Introduction They are typically located on the same DNA as the gene they control (cis) CRM includes, but not limited to the following  Locus control regions  Promoters  Enhancers  Silencers  Boundary  Control elements and  Other modulators Eläinlääketieteellinen tiedekunta / Henkilön nimi / Esityksen nimi www.helsinki.fi/yliopisto 1.11.2018 3

Typical examples in understanding gene expression The development of animals from zygote to adults requires the expression of a specific set of genes at each developmental stage Eläinlääketieteellinen tiedekunta / Henkilön nimi / Esityksen nimi www.helsinki.fi/yliopisto 1.11.2018 4

The differentiation of cells into distinct tissues and organs also requires the expression of a specific set of genes in each cell types Eläinlääketieteellinen tiedekunta / Henkilön nimi / Esityksen nimi www.helsinki.fi/yliopisto 1.11.2018 5

Gene expression Eläinlääketieteellinen tiedekunta / Henkilön nimi / Esityksen nimi www.helsinki.fi/yliopisto 1.11.2018 6

Importance of CRM 1. Expand our understanding of biology 2. Application in medicine (susceptibility to diseases) 3. Proper understanding of evolution Eläinlääketieteellinen tiedekunta / Henkilön nimi / Esityksen nimi www.helsinki.fi/yliopisto 1.11.2018 7

Methods used in predicting CRM in animals 1. Searching genomic DNA for clusters of motifs that are needed for the specific binding of transcription factors 2. Comparing homologous, non-coding DNA sequences between related species 3. Direct assays for DNA sequences with epigenetic features that are characteristic of regulatory regions Eläinlääketieteellinen tiedekunta / Henkilön nimi / Esityksen nimi www.helsinki.fi/yliopisto 1.11.2018 8

Information to help understand the methods http://www.ncbi.nlm.nih.gov/PMGifs/Genomes/micr.html • The whole-genome sequences for over 85 microorganisms • Humans, and a handful of other eukaryotic organisms Combination of results from database similarity searches and gene-predicting algorithms to identify coding sequences with good but not complete accuracy Eläinlääketieteellinen tiedekunta / Henkilön nimi / Esityksen nimi www.helsinki.fi/yliopisto 1.11.2018 9

Eläinlääketieteellinen tiedekunta / Henkilön nimi / Esityksen nimi www.helsinki.fi/yliopisto 1.11.2018 10

Softwares Eläinlääketieteellinen tiedekunta / Henkilön nimi / Esityksen nimi www.helsinki.fi/yliopisto 1.11.2018 11

How is this done? Eläinlääketieteellinen tiedekunta / Henkilön nimi / Esityksen nimi www.helsinki.fi/yliopisto 1.11.2018 13

Methods used in predicting CRM in animals 1. Searching genomic DNA for clusters of motifs that are needed for the specific binding of transcription factors Eläinlääketieteellinen tiedekunta / Henkilön nimi / Esityksen nimi www.helsinki.fi/yliopisto 1.11.2018 14

2. Comparing homologous, non-coding DNA sequences between related species By comparing the genomic sequences of species at different evolutionary distances, one can identify coding sequences and conserved non-coding sequences with regulatory functions and determine which sequence are unique for a given specie www.helsinki.fi/yliopisto 1.11.2018 17

3. Direct assays for DNA sequences with epigenetic features that are characteristic of regulatory regions Epigenetic features are reversible features on a cell’s DNA that affect gene expression without altering DNA It is based on high-throughput sequencing and mapping to reference genomes Eläinlääketieteellinen tiedekunta / Henkilön nimi / Esityksen nimi www.helsinki.fi/yliopisto 1.11.2018 19

Pros and cons Comparing homologous, Searching genomic DNA for Direct assays for DNA clusters of motifs that are non-coding DNA sequences sequences with needed for the specific between related species epigenetic features that binding of transcription are characteristic of factors regulatory regions 1. Partial success under 1. Partial success under favourable conditions favourable conditions 2. Only small subset of CRMs is 2. Only small subset of CRMs is likely to be discovered by likely to be discovered by extreme evolutionary 1. Epigenetic marks must be extreme evolutionary constraint constraint mapped in tissues and at 3. Does not work equally in all times of development that 3. Does not work equally in all tissues are informative to the tissues question at hand 4. No sufficient specificity 4. No sufficient specificity 2. May be bias. 5. Not designed to find CRMs that 5. Not designed to find CRMs are active in only 1 specie or that are active in only 1 that are changing in a lineage specie or that are changing in specific manner a lineage specific manner Eläinlääketieteellinen tiedekunta / Henkilön nimi / Esityksen nimi www.helsinki.fi/yliopisto 1.11.2018 21

Summary/conclusion • Cis -regulatory modules are DNA sequence required to regulate gene expression • The genome of both prokaryotes and eukaryotes are available in a vast number of databases • These databases are used to predict the DNA sequence required for gene expression by different methods Eläinlääketieteellinen tiedekunta / Henkilön nimi / Esityksen nimi www.helsinki.fi/yliopisto 1.11.2018 22

Summary/conclusion Given the limitations of methods based on sequence motifs and comparative genomics, direct measurement of diagnostic epigenetic features should lead to improved methods for CRM prediction. Particular epigenetic features are highly correlated with CRMs, and progress is being made in finding combinations of these features that may distinguish different types of CRM. Eläinlääketieteellinen tiedekunta / Henkilön nimi / Esityksen nimi www.helsinki.fi/yliopisto 1.11.2018 23

Genomic approaches towards finding cis -regulatory modules (CRM) in - PowerPoint PPT Presentation

Genomic approaches towards finding cis -regulatory modules (CRM) in animals Matthew I. Omoruyi 21.01.2013 www.helsinki.fi/yliopisto 1.11.2018 1 Introduction CRM is a stretch of DNA, usually 100 1000 DNA base pairs in length, where a

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Genomic approaches towards finding cis -regulatory modules (CRM) in - PowerPoint PPT Presentation

Genomic approaches towards finding cis -regulatory modules (CRM) in animals Matthew I. Omoruyi 21.01.2013 www.helsinki.fi/yliopisto 1.11.2018 1 Introduction CRM is a stretch of DNA, usually 100 1000 DNA base pairs in length, where a

Finding a Better Way: Genomic Distinctiveness Kyle B. Brothers Genomics and Ethics in Research

International Regulatory Cooperation The range of possible approaches Cline Kauffmann, Deputy

Integration of Genetic and Integration of Genetic and Genomic Approaches for the Genomic

A comparative study of Gaussian Graphical Model approaches for genomic data Roberto Anglani

of Regulatory Network Ping Ma Department of Statistics &amp; Institute for Genomic Biology

Big data approaches in cardiovascular genomic research Randal Westrick CDaS and Department of

Ask and You Shall Receive: Empirically Evaluating Declarative Approaches to Finding Data in

UTR cis-regulatory modules Eliana Salvemini Department of Computer Science University of Bari

Regulatory approaches to application of biosolids to agricultural land in Australia and New

Genomic Knowledge Standards (GKS) genomicsandhealth.org Genomic Knowledge Standards GKS aims

The scientific and regulatory approaches to facilitating disease-modifying drug development and

Regulatory interactions: Expectations on extrapolation approaches Lynne Yao, M.D. Director,

Using the genomic relationship matrix to predict the accuracy of genomic selection M.E. Goddard

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Privacy in the Genomic Era XiaoFeng Wang, IUB http://www.informatics.indiana.edu/xw7 Genomic

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