AL-Base: a Visual Platform Analysis Tool for the Study of Amyloidogenic Immunoglobulin Light Chain Sequences

Overview

Journal Amyloid

Specialty Biochemistry

Date 2009 Mar 18

PMID 19291508

Citations 46

Authors

Kip Bodi

Tatiana Prokaeva

Brian Spencer

Maurya Eberhard

Lawreen H Connors

David C Seldin

Affiliations

Soon will be listed here.

Abstract

AL-Base, a curated database of human immunoglobulin (Ig) light chain (LC) sequences derived from patients with AL amyloidosis and controls, is described, along with a collection of analytical and graphic tools designed to facilitate their analysis. AL-Base is designed to compile and analyse amyloidogenic Ig LC sequences and to compare their predicted protein sequence and structure to non-amyloidogenic LC sequences. Currently, the database contains over 3000 de-identified LC nucleotide and amino acid sequences, of which 433 encode monoclonal proteins that were reported to form fibrillar deposits in AL patients. Each sequence is categorised according to germline gene usage, clinical status and sample source. Currently, tools are available to search for sequences by various criteria, to analyse the biochemical properties of the predicted amino acids at each position and to display the results in a graphical fashion. The likelihood that each sequence has evolved through somatic hypermutation can be predicted using an automated binomial or multinomial distribution model. AL-Base is available to the scientific community for research purposes.

Citing Articles

Seeking Amyloidosis Very Early: Free light Chain Differentials and IGLV Gene Use as Screening Variables for Light-chain Amyloidosis in λ Monoclonal Gammopathies.

Zhou P, Mansukhani M, Yeh R, Lu J, Xia H, Koganti L Br J Cancer Res. 2025; 7(2):681-686.

PMID: 39790465 PMC: 11711923. DOI: 10.31488/bjcr.193.

Predicting Structural Consequences of Antibody Light Chain N-Glycosylation in AL Amyloidosis.

Morgan G, Yung Z, Spencer B, Sanchorawala V, Prokaeva T Pharmaceuticals (Basel). 2024; 17(11).

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Aggregating amyloid resources: A comprehensive review of databases on amyloid-like aggregation.

Iglesias V, Chilimoniuk J, Pintado-Grima C, Barcenas O, Ventura S, Burdukiewicz M Comput Struct Biotechnol J. 2024; 23:4011-4018.

PMID: 39582896 PMC: 11585477. DOI: 10.1016/j.csbj.2024.10.047.

Prediction and Evaluation of Protein Aggregation with Computational Methods.

Hassan M, Shahzadi S, Li M, Kloczkowski A Methods Mol Biol. 2024; 2867:299-314.

PMID: 39576588 DOI: 10.1007/978-1-0716-4196-5_17.

An updated AL-Base reveals ranked enrichment of immunoglobulin light chain variable genes in AL amyloidosis.

Morgan G, Nau A, Wong S, Spencer B, Shen Y, Hua A bioRxiv. 2024; .

PMID: 39314448 PMC: 11419035. DOI: 10.1101/2024.09.11.612490.

References

Higgins D, Sharp P . CLUSTAL: a package for performing multiple sequence alignment on a microcomputer. Gene. 1988; 73(1):237-44. DOI: 10.1016/0378-1119(88)90330-7. View

Alexanian R, Fraschini G, Smith L . Amyloidosis in multiple myeloma or without apparent cause. Arch Intern Med. 1984; 144(11):2158-60. View

Lefranc M, Pommie C, Kaas Q, Duprat E, Bosc N, Guiraudou D . IMGT unique numbering for immunoglobulin and T cell receptor constant domains and Ig superfamily C-like domains. Dev Comp Immunol. 2004; 29(3):185-203. DOI: 10.1016/j.dci.2004.07.003. View

Bellotti V, Merlini G, Bucciarelli E, Perfetti V, Quaglini S, Ascari E . Relevance of class, molecular weight and isoelectric point in predicting human light chain amyloidogenicity. Br J Haematol. 1990; 74(1):65-9. DOI: 10.1111/j.1365-2141.1990.tb02539.x. View

Dobson C . Experimental investigation of protein folding and misfolding. Methods. 2004; 34(1):4-14. DOI: 10.1016/j.ymeth.2004.03.002. View

Lefranc M, Pommie C, Ruiz M, Giudicelli V, Foulquier E, Truong L . IMGT unique numbering for immunoglobulin and T cell receptor variable domains and Ig superfamily V-like domains. Dev Comp Immunol. 2002; 27(1):55-77. DOI: 10.1016/s0145-305x(02)00039-3. View

Pearson W, Lipman D . Improved tools for biological sequence comparison. Proc Natl Acad Sci U S A. 1988; 85(8):2444-8. PMC: 280013. DOI: 10.1073/pnas.85.8.2444. View

Zimmerman J, Eliezer N, Simha R . The characterization of amino acid sequences in proteins by statistical methods. J Theor Biol. 1968; 21(2):170-201. DOI: 10.1016/0022-5193(68)90069-6. View

Perfetti V, Casarini S, Palladini G, Vignarelli M, Klersy C, Diegoli M . Analysis of V(lambda)-J(lambda) expression in plasma cells from primary (AL) amyloidosis and normal bone marrow identifies 3r (lambdaIII) as a new amyloid-associated germline gene segment. Blood. 2002; 100(3):948-53. DOI: 10.1182/blood-2002-01-0114. View

10.

Solomon A, Frangione B, FRANKLIN E . Bence Jones proteins and light chains of immunoglobulins. Preferential association of the V lambda VI subgroup of human light chains with amyloidosis AL (lambda). J Clin Invest. 1982; 70(2):453-60. PMC: 371254. DOI: 10.1172/jci110635. View

11.

Kawashima S, Ogata H, Kanehisa M . AAindex: Amino Acid Index Database. Nucleic Acids Res. 1998; 27(1):368-9. PMC: 148186. DOI: 10.1093/nar/27.1.368. View

12.

Bhaskaran R, Ponnuswamy P . Dynamics of amino acid residues in globular proteins. Int J Pept Protein Res. 1984; 24(2):180-91. DOI: 10.1111/j.1399-3011.1984.tb00944.x. View

13.

Stevens F . Four structural risk factors identify most fibril-forming kappa light chains. Amyloid. 2000; 7(3):200-11. DOI: 10.3109/13506120009146835. View

14.

Stevens F, Argon Y . Pathogenic light chains and the B-cell repertoire. Immunol Today. 1999; 20(10):451-7. DOI: 10.1016/s0167-5699(99)01502-9. View

15.

Comenzo R, Wally J, Kica G, Murray J, Ericsson T, Skinner M . Clonal immunoglobulin light chain variable region germline gene use in AL amyloidosis: association with dominant amyloid-related organ involvement and survival after stem cell transplantation. Br J Haematol. 1999; 106(3):744-51. DOI: 10.1046/j.1365-2141.1999.01591.x. View

16.

Janin J, Wodak S . Conformation of amino acid side-chains in proteins. J Mol Biol. 1978; 125(3):357-86. DOI: 10.1016/0022-2836(78)90408-4. View

17.

Ganapathiraju M, Manoharan V, Klein-Seetharaman J . BLMT: statistical sequence analysis using N-grams. Appl Bioinformatics. 2005; 3(2-3):193-200. DOI: 10.2165/00822942-200403020-00013. View

18.

Yu C, Zavaljevski N, Stevens F, Yackovich K, Reifman J . Classifying noisy protein sequence data: a case study of immunoglobulin light chains. Bioinformatics. 2005; 21 Suppl 1:i495-501. DOI: 10.1093/bioinformatics/bti1024. View

19.

Gu M, Wilton R, Stevens F . Diversity and diversification of light chains in myeloma: the specter of amyloidogenesis by proxy. Contrib Nephrol. 2006; 153:156-81. DOI: 10.1159/000096766. View

20.

PONTIUS J, RICHELLE J, Wodak S . Deviations from standard atomic volumes as a quality measure for protein crystal structures. J Mol Biol. 1996; 264(1):121-36. DOI: 10.1006/jmbi.1996.0628. View