Genomics Services

The Genomics Services Laboratory (GSL; previously known as the Biomedical Genomics Core) has extensive expertise in multiple aspects of genomics analysis, including consultation and assistance with experimental design, quality control of starting material (DNA or RNA), library preparation and multiple techniques for next-generation sequencing analysis. Several of our services include basic data analysis and advanced bioinformatics analysis and are provided on a collaborative basis.

We are an official core facility of The Research Institute at Nationwide Children's Hospital. As part of the Institute for Genomic Medicine, the GSL is a comprehensively equipped facility offering services to both internal and external investigators.

The core is equipped with multiple Next-Generation Sequencing (NGS) systems. These include two Illumina HiSeq 4000 sequencing instruments, each capable of producing over 900 billion base pairs (900 GB) of sequence data per run, enabling us to sequence 12 human genomes at 30X coverage in a single 3-day instrument run. In addition, the laboratory employs an Illumina MiSeq which can rapidly produce up to 15 GB of 2 X 300 base pair reads in 40 hours, as well as an Illumina MiniSeq capable of generating 7.5 GB of 2x150 base pairs in approximately 24 hours. Additionally, the laboratory operates the Pacific Biosciences Sequel sequencing systems which are ideal for de novo whole genome sequencing, generating read lengths in excess of 20 kb and upwards of 5 Gb of data per SMRT cell. These instruments are housed and operated in our CLIA laboratory space.

All of these technologies are being utilized by our research investigators for multiple application. These include: human genome re-sequencing studies for rare variant discovery and structural variation analysis (both targeted capture and whole genome), somatic mutation profiling (e.g. comprehensive analysis of tumor and matched genomes), gene expression and transcriptome analysis (RNA-Seq and miRNA-Seq of both eukaryotes and prokaryotes), epigenomic studies including DNA-Protein interaction analysis (ChIP-Seq, ATAC-Seq) and methylation analysis (Methyl-Seq), metagenomics, and de novo genome sequencing and assembly for viral, bacterial and eukaryotic genomes.

Services

Whole Genome Sequencing Services (WGS)

We provide whole genome sequencing for interrogating single-nucleotide variants (SNVs), insertions and deletions (indels), structural variants (SVs), and copy number variants (CNVs) in coding and non-coding regions of the genome. We also offer 10X Genomics Chromium Genome “linked read” library preps and sequencing for human genomes. Analysis is performed using 10X Genomics software, applications include human haplotype phasing and structural variant detection. Service includes DNA QC, library prep, and sequencing on Illumina HiSeq 4000 using paired-end 150 base-pairs reads.

  • WGS sequence to yield 30X coverage

  • WGS sequence to yield 60X coverage

  • 10XG WGS sequence to yield 40X coverage

Whole Exome Services

Whole exome sequencing for targeting only the coding regions of the genome allows for a cost-effective approach to determine genetic variations in genes most likely to affect phenotype.  Library preparation and the enrichment methods offered include: Agilent Exome Capture and Integrated DNA Technologies xGen Lockdown Probes. Service includes DNA QC, library prep, exome capture, and sequencing on Illumina HiSeq 4000 using paired-end 150 base-pairs reads.

WES Sequencing Coverage

  • Sequence to yield 100-150X coverage

  • Sequence to yield higher coverage > 250X coverage

RNA Sequencing Services

Total RNA-Seq measures gene and transcript abundance, and identifies known and novel features of the transcriptome. Small RNA sequencing (RNA-Seq) allows for the isolation and sequencing of small RNA species, such as microRNAs (miRNAs). Service includes RNA QC, library preparation, and sequencing on the variety of available Illumina sequencers appropriate to library type and species of RNA.

  • Total RNA-Seq - The services includes rRNA depletion using ribosomal RNA probes (Rib0-Zero chemistry), Truseq Total RNA Stranded library prep and sequencing 150 base-pair reads to yield 60 million to 80 million reads per sample using Illumina HiSeq 4000. This service is for differential expression of RNA from Human/Rat/Mouse organisms. RNA-seq is available for other non-human organisms.  

  • miRNA-Seq - The service includes RNA QC, NEB Next Small RNA library prep. Upon consultation, the appropriate Illumina platform and base pair read length will be determined to generate ~2-5 million reads per sample for differential expression analysis.

Sequencing Only Services

  • Hiseq 4000 Paired-end 150 base-pair reads - Customer supplies prepared and pooled libraries along with the sample information and approved QC report. Fastq data will be delivered upon completion of the project.

  • Miseq Paired-end 300 base-pair reads - Customer supplies prepared and pooled libraries along with the sample information and approved QC report.  Fastq data will be delivered upon completion of the project.

Custom Bioinformatics Service

Hourly consulting charge for custom bioinformatics projects.

Instrumentation

  • Illumina Sequencing Technologies: Massively parallel, short read, sequencing instruments that are able to decipher billions of DNA bases in short stretches (i.e., 100-300 base paired read lengths).

    • HiSeq 4000

    • MiSeq

    • MiniSeq

    • NovaSeq (coming soon)

  • Pacific Biosciences: Single Molecule Real Time (SMRT) sequencing instrument capable of sequencing long DNA molecules with average read lengths (DNA stretches) of 15,000 bases. Sequencing reactions occur in low volume (25 zl) zero-mode waveguides (ZMW).

    • Sequel

  • 10X Genomics: A droplet-based microfluidics technology enabling sequencing of long molecules (similar to Pacific Biosciences) using short read sequencing technologies such as Illumina.

  • Oxford Nanopore: A nanopore sequencing technology

    • Minion

Bioinformatics Analysis

The IGM Computational Genomics Group has partnered with the GSL to provide the substantial technical and bioinformatics expertise required to oversee the multiple platforms that acquire, store and analyze large and complex genomic data sets. The Translational Bioinformatics Team provides bioinformatics services on a collaborative basis at subsidized hourly rates and serves as an interface between the research investigator and the multiple domains that are required to handle the size and complexity of genomic data. IGM has built a dedicated, cloud-based computational resource through Amazon Web Services (AWS), allowing large HPC or Hadoop clusters with hundreds of instances to be provisioned on demand, enabling us to support the analysis needs of both large and small scale sequencing projects. We are uniquely positioned to adapt and develop new computational tools in a manner that is driven by the demands of our research community as it utilizes new technologies. 

The Computational Genomics Group has developed state of the art analytical pipelines for NGS analysis including, but not limited to, transcriptomics (RNA-Seq and miRNA-Seq), whole genome sequencing (WGS), whole exome sequencing (WES) and paired tumor-normal somatic variant detection. Through development of the balanced parallelization strategy for human genome analysis (named “Churchill”), we were successfully able to reduce the time taken to go from raw sequencer output to final variant calls from days to under two hours, enabling both rapid and accurate identification of disease causing genetic variants in germline and cancer samples. In addition to developing our own bioinformatics tools, the unit also evaluates and supports multiple software products for genomics applications that are designed to make data analysis tools accessible to biologists.

IGM GSL Acknowledgment Policy

Our facility does not expect authorship on studies using data generated on a fee-for-service basis. However, fee-for-service reimbursement for bioinformatics support does not alter the contribution to the academic enterprise, and co-authorship should be considered. Fee-for-service bioinformatics support is simply an alternative to salary support as would be provided by serving as a co-investigator on an NIH grant, for example. Consideration for authorship should be based on the accepted criteria of most medical journals with the contribution of each person being evaluated as a manuscript is prepared. These criteria generally cite both study design and bioinformatics analysis as intellectual input sufficient for authorship. It is impossible to define every situation in advance; however, it should be clear that reimbursement for time does not preclude or replace authorship.

Suggested Acknowledgement:

Methods: “[Service] was performed by the Biomedical Genomics Core of The Research Institute at Nationwide Children’s Hospital, Columbus, Ohio”

Acknowledgements: “We thank [name(s) of personnel] of the Biomedical Genomics Core of the Research Institute at Nationwide Children’s Hospital, Columbus, Ohio for their help with [help provided]”