UMass

ALS Variant Server (AVS)

Auxologico

Welcome to the ALS Variant Server (AVS)

The goal of the ALS Variant Server is to provide researchers with a database of variants identified from exome sequencing of ALS cases. It is our hope that these results will increase the efficiency of researchers to identify ALS-associated genes and reduce false-positives.

This web site was conceived and developed by researchers at the University of Massachusetts Medical School (Worcester, MA) and the IRCCS Istituto Auxologico Italiano - Università degli Studi di Milano (Milan, Italy).

Additional assistance and data was provided by:

This design and layout of this website is strongly modeled from the NHLBI Exome Sequencing Project. We would like to thank the contributors of this project for their excellent work.

About

In order to increase the speed in which the scientific community identifies ALS-associated genes, we have taken the step to create this publicly available database of exome sequences from ALS samples. Researchers identify candidate genes for ALS by a variety of methods (e.g. expression analysis). However, to further investigate these genes, researchers often have to obtain a large number of ALS samples and then sequence these candidate genes. This approach can be extremely expensive and thus cost-prohibitive to the advancement of ALS genetic research. This does not take into account the time and labor needed to investigate such genes. Furthermore, there is an inherent redundancy for the scientific community with this approach that ends up wasting research money. By creating a public database of ALS samples, researchers can now investigate their gene of interest within minutes at no cost whatsoever. This will allow researchers to focus on those genes with the greatest promise and not waste money, time and labor on potential false leads. The current version of the ALS Variant Server consists of ~275 sporadic ALS cases. However, we anticipate expanded this set to over ~1300 in the coming year. Additionally, we anticipate expanding our database to include familial ALS cases.

Contributors

Database/Website Design and Data Analysis

Sample Preparation

Data Usage and Release

We request that any data obtained from this website be cited in publications.

Citation

ALS Variant Server, Worcester, MA (URL: http://als.umassmed.edu/) [date (month, yr) accessed].

Acknowledgement for Publication

The authors would like to thank the ALS Variant Server (als.umassmed.edu) which is supported by funds from NIH/NINDS (1R01NS065847), AriSLA (EXOMEFALS, NOVALS), the ALS Association, and the Motor Neurone Disease Association.

Permission and Terms of Use

This web site is intended to provide results from exome sequencing data of ALS samples. The contents of the AVS is intended strictly for educational and research purposes. The data derived from this website may not be used for any commercial purpose. The data from this website may not be replicated on any other website.

How to Use

Data from the AVS may only be searched at the gene level at this time. Enter the gene name of interest in the text box and click "search". Output columns may be sorted by clicking the appropriate column header. Rows are coloured based on the general variant type. The output may also be exported to a tab-delimited file.

Contact and FAQ

If you have questions concerning the AVS, please read the FAQs below. If you have additional questions, please contact john.landers@umassmed.edu.

What is the source of the samples present on the AVS?

Exome sequencing results on the AVS are derived from ~277 sporadic ALS cases from the United States and Italy.

Is data available for individual samples?

Currently, sample level data is not available for individual samples.

Are INDELs included in the AVS?

At the present time, we have elected to not include INDELs in the AVS and focus strictly on single nucleotide polymorphisms.

What methods were used to generate the data present on the AVS?

Samples were aligned to a human reference (hg19) using BWA (Burrows-Wheeler Aligner). Data was processed using the Genome Analysis ToolKit (GATK). All aligned data was subjected to “duplicate removal”, index realignment (GATK IndelRealigner), and base quality recalibration (GATK TableRecalibration). Variant detection and genotyping were performed using the UnifiedGenotyper (UG) tool from GATK, and only performed on the targeted exome regions. Variant data for each sample was formatted (variant call format[VCF]) as “raw” calls for all samples, and lower quality/false positives sites were flagged using the filtration walker (GATK) (low quality scores (≤50), allelic imbalance (≥0.75), long homopolymer runs (>3), and/or low quality by depth <5). Quality control parameters included the total number of reads, coverage distribution, gender concordance, Ti/Tv ratio, and homozyogozity/heterozygozity rates. The results were annotated using SnpEff (http://snpeff.sourceforge.net).

I would like to contribute sample DNA or data to your project. Who should I contact?

Please contact us at john.landers@umassmed.edu.