Welcome to the Computational Research and Development Group (CRD) homepage. We are part of the Genome Sequencing and Analysis Program at the Broad Institute. This site presents tools we have developed for genome assembly and variant detection. If you have any trouble using them, please write to us at crdhelp@broadinstitute.org, and see also our general build help. We thank the National Human Genome Research Institute and National Institute of Allergy and Infectious Diseases for supporting the development of these tools.

Genome assembly

Our goal is to produce high-quality draft sequences at low cost. To do this, we look for the optimal deployment of cutting-edge sequencing technologies and assembly algorithms.

• ALLPATHS-LG (download,manual,blog) is the method we recommend and use currently. It works on both small and large (mammalian size) genomes. To use it, you should first generate ~100 base Illumina reads from two libraries: one from ~180 bp fragments, and one from ~3000 bp fragments, both at about 45x coverage. Sequence from longer fragments will enable longer-range continuity.
  
  Gnerre S, MacCallum I, Przybylski D, Ribeiro F, Burton J, Walker B, Sharpe T, Hall G, Shea T, Sykes S, Berlin A, Aird D, Costello M, Daza R, Williams L, Nicol R, Gnirke A, Nusbaum C, Lander ES, Jaffe DB. 2010. High-quality draft assemblies of mammalian genomes from massively parallel sequence data. Proceedings of the National Academy of Sciences USA (epub ahead of print, Dec. 27, 2010).
• ALLPATHS (download,manual) is the predecessor of ALLPATHS-LG. It works on ~30 base reads. [Superceded by ALLPATHS-LG; unsupported.]
  
  Butler J, MacCallum I, Kleber M, Shlyakhter IA, Belmonte MK, Lander ES, Nusbaum C, Jaffe DB. 2008. ALLPATHS: de novo assembly of whole-genome shotgun microreads. Genome Research 18: 810–20.
  
  MacCallum I, Przybylski D, Gnerre S, Burton J, Shlyakhter I, Gnirke A, Malek J, McKernan K, Ranade S, Shea TP, Williams L, Young S, Nusbaum C, Jaffe DB. 2009. ALLPATHS 2: small genomes assembled accurately and with high continuity from short paired reads. Genome Biology 10: R103.
• ARACHNE (download,manual) was designed for long Sanger-chemistry reads.
  
  Batzoglou S, Jaffe DB, Stanley K, Butler J, Gnerre S, Mauceli E, Berger B, Mesirov JP, Lander ES. 2002. ARACHNE: a whole-genome shotgun assembler. Genome Research 12: 177–189.
  
  Jaffe DB, Butler J, Gnerre S, Mauceli E, Lindblad-Toh K, Mesirov JP, Zody MC, Lander ES. 2003. Whole-genome sequence assembly for mammalian genomes: Arachne 2. Genome Research 13: 91–96.
  
  Gnerre S, Lander ES, Lindblad-Toh K, Jaffe DB. 2009. Assisted assembly: how to improve a de novo genome assembly by using related species. Genome Biology 10: R88.

Genome variant detection

• VAAL (download,manual) VAAL is a variant ascertainment algorithm that can be used to detect SNPs, indels, and more complex genetic variants. On bacterial data sets, it achieves very high sensitivity, and near perfect specificity. VAAL can be used to compare reads from one strain to a reference sequence from another strain. It can also be used to compare reads from two strains to each other, using a third strain to determine homology. For example, we have used VAAL to find a single mutation responsible for bacterial resistance: the output of the program was that single mutation and no others. VAAL uses an assisted assembly algorithm that borrows from ALLPATHS.
  
  Nusbaum C, Ohsumi TK, Gomez J, Aquadro J, Victor TC, Warren RM, Hung DT, Birren BW, Lander ES, Jaffe DB. Jan 2009. Sensitive, specific polymorphism discovery in bacteria using massively parallel sequencing. Nature Methods 6: 67–9.
• SWAP454 (download,manual) is a program for calling SNPs using 454 read data. SWAP454 also includes code for creating improved quality scores for 454 read data that has been incorporated into the algorithm used by 454 Life Sciences.
  
  Brockman W, Alvarez P, Young S, Garber M, Giannoukos G, Lee WL, Russ C, Lander ES, Nusbaum C, Jaffe DB. 2008. Quality scores and SNP detection in sequencing-by-synthesis systems. Genome Research 18: 763–770.
• SomaticCall (download,manual) SomaticCall is a program that finds single-base differences (substitutions) between sequence data from tumor and matched normal samples. It takes as input a BAM file for each sample, and produces as output a list of differences (somatic mutations). [We plan to remove this code from the site. Let us know if this would be a problem for you. SomaticCall is no longer under active development and we believe that better programs are available, notably MuTect, from Kris Cibulskis, kcibul (at) broadinstitute (dot) org.]