Scott Emrich

Assistant Professor, Computer Science and Engineering

Scientific Manager, VectorBaseUniversity of Notre Dame

A flexible, scalable genomics framework for integrating

heterogeneous vector sequence data

Assembly required…

VectorBase is here to help (esp. –OMICs data)

Please see me and/or Dan Lawson (EBI) anytime this meeting

Anopheles gambiae M & S

Lawnziak, Emrich et al. (2010, Science)

Some genomic regions display footprint of strong, recent selection

Lawniczak, Emrich et al. 2010 Science

A C G T C G T T A C T G CReference:

A C G T C G A T A C T G CSample_1:

A C G T C G T T A T T G CSample_2:

A C G T C G A T A T T G CA C G T C G A T A T T G CA C G T C G A T A C T G CA C G T C G A T A C T G C

A C G T C G T T A T T G CA C G T C G T T A T T G CA C G T C G T T A T T G CA C G T C G T T A T T G C

FlexReseq tool for integrating diverse sequence data

FlexReseq implementation

Genome Analysis Toolkit (GATK):Map-Reduce framework that allows efficient access to large resequencing data sets

FlexReseq: A module for GATK:Configurable interface allows easy data explorationModular implementation of rules allows for easy extension of software

Saves you from lots of scripting (Perl) code!

McKenna et al., Genome Research, 2010

A malaria use-case for FlexReseq

Samarakoon, Regier, et al., BMC Genomics, 2011

Why are some parasites drug-resistant?

Goal: we want to connect genotype (genome)

to phenotype (drug response)

How did drug-resistance evolve?

1. Whole genome shotgun

sequencing 2. Reference genome mapping

NCBI Trace Archive [28]

Reference genome

(3D7)

Parental genomes[shotgun libraries]

Progeny genomes[shotgun libraries]

PlasmoDB (v5.4) [27]

Mapped:

SSAHA2

http://www.sanger.

ac.uk

ParentsHB3, Dd2

Progenyrecombinants

SC05 7C126

Shotgun librariesGS-FLX technology

454/Roche

Genetic crossWellems et al.

1990 [24]

A more detailed map of P. falciparum

Dd2 HB3Chromosome position

1

2

3

4

5

6

7

8

9

10

11

12

13

14

Chr

omos

om

e

(A) 7C126 (B) SC05

Association of 2La with clines of aridity in Nigeria…

Modified from Coluzzi et al (1979)

24,000 mosquitoes

194 sampling localities

High-throughput sequencing

• Data from Besansky lab• Illumina Genome

Analyzer• 4 population pools

(S-form)• SHRiMP alignment• BWA works also

C. Cheng et al, unpublished

Differential mapping biases do exist

Population haplotyping

In situ error isolation

Has been shown to be important in ancient DNA-based ecology

Thanks to…

VectorBase (NIH/NIAID)• Dr. Nora Besansky (ND)• Dr. Frank Collins (ND)• Rory Carmichael, Andrew

Shehan, Nate Konopinski, Dave Campbell (ND), others…

Notre Dame Bioinformatics Lab, Summer 2010

Anopheles genome cluster groupi5KArthropod Genomics Consortium steering committee