Brief Description
JoinSolver matches
immunoglobulin sequences to a database of germlines to help elucidate the
underlying recombination mechanism that yields a highly diverse repertoire of
immunoglobulin antigen binding sites. It is the first application of its kind to
use a consecutive scoring algorithm, which we believe simulates the underlying
biology closer than other scoring systems.
Caption: This figure shows part of a typical JOINSOLVER®
result (sequence accession number Z80479).
First, JOINSOLVER® returns a summary of the
rearrangement
results. After the summary, a
base-by-base alignment of the input sequence to the highest scoring V,
D, and J
germline sequences are returned.
Optional analyses, such as Junction and Mutation Analyses, are
available.
List of Collaborators
Peter Lipsky, M.D. Chief, Autoimmunity Branch, National Institute on Arthritis and Musculoskeletal
Nancy Longo, Ph.D. Postdoctoral Fellow, NIAMS. Autoimmunity Branch, Repertoire Analysis Group.
Major Accomplishments of this
Activity in FY 2007
In 2007, we concentrated on improving the quality and the format of the results. JoinSolver has a new method for scoring germ-line matches. The new scoring method allows JoinSolver to handle sequences that are lightly mutated. The results from simulating hundreds of thousands of V(D)J recombination events show an improvement in the JoinSolver’s ability to identify a germ-line and the germ-line’s start and end points.
Anticipated Major Accomplishments of this Activity in FY 2008:
We plan to publish the new scoring algorithm and the results of the simulation. When the paper is accepted, JoinSolver will re-enter production mode. Additional analyses can be added, such as a hydropathy analysis which calculates the hydrophobicity and hydrophilicity of immunoglobulin along the sequence.
Metrics
• Sequences analyzed since April 2007: 61,194
• Number of citations: 7
Scientific Impact
Using JoinSolver, scientists can analyze thousands of immunoglobulin DNA sequence. Around the world, scientists are using JoinSolver to study immune deficiency diseases such as chronic granulomatous disease, systemic lupus erythematosus, and autoimmune lymphoproliferative disease syndrome. New applications that mimic the features currently available on JoinSolver are being developed. Several projects, such as iHMMume-align, SoDA and JoinML are comparing their results against JoinSolver to prove their credentials. JoinSolver is still the fastest algorithm available to analyze immunoglobulin sequences for recombination events. JoinSolver is still the only algorithm that uses a consecutive base-matching scoring algorithm, which we believe produces the best results.
Recent Citations
B.A. Gaëta, H.R. Malming, K.J.L. Jackson, M.E. Bain, P. Wilson, A.M. Collins, ”iHMMume-align: hidden Markov model-based alignment and identification of germline genes in rearranged immunoglobulin gene sequences”, Bioinformatics, 23(13), 1580-1587, 2007.
J.M Murray, J.P. O'Neill, T. Messier, J. Rivers, V.E. Walker, B. McGonagle, L. Trombley, L.G. Cowell, G. Kelsoe, F. McBlane, B.A. Finette, “V(D)J recombinase-mediated processing of coding junctions at cryptic recombination signal sequences in peripheral T cells during human development”, Journal of Immunology, 177(8). 5393-5404, October, 15 2006.
U. Andreasson, S. Flicker, M. Lindstedt, R. Valenta, L. Greiff, M. Korsgren, C.A.K Borrebaeck, M. Ohlin, “The human IgE-encoding transcriptome to assess antibody repertoires and repertoire evolution”, Journal of Molecular Biology, 362(2), 212-227, September 15, 2006.
L. Ohm-Laursen, M. Nielsen, S.R. Larsen, T. Barington, “No evidence for the use of DIR, D-D fusions, chromosome 15 open reading frames or V(H)replacement in the peripheral repertoire was found on application of an improved algorithm, JointML, to 6329 human immunoglobulin H rearrangements”, Immunology, 119(2), 265-277, October 2006.
L.C. Watson, C.S. Moffatt-Blue, R.Z. McDonald, E. Kompfner, D. Ait-Azzouzene, D. Nemazee, A.N. Theofilopoulos, D.H. Kono, A.J. Feeney. “Paucity of V-D-D-J rearrangements and V-H replacement events in lupus prone and nonautoimmune TdT(-/-) and TdT(+/+) mice”, Journal of Immunology, 177(2), 1120-1128, July 15, 2006.
J.J. Bleesing, M.M. Souto-Carneiro, W.J. Savage, M.R. Brown, C. Martinez, S. Yavuz, S. Brenner, R.M. Siegel, M.E. Horwitz, P.E. Lipsky, H.L, Malech, T.A. Fleisher, “Patients with chronic granulomatous disease have a reduced peripheral blood memory B cell compartment”, Journal of Immunology, 176(11), 7096-7103, June 1, 2006.