Lineage tree analysis of immunoglobulin variable-region gene mutations in autoimmune diseases: chronic activation, normal selection

Autoimmune diseases show high diversity in the affected organs, clinical manifestations and disease dynamics. Yet they all share common features, such as the ectopic germinal centers found in many affected tissues. Lineage trees depict the diversification, via somatic hypermutation (SHM), of immunoglobulin variable-region (IGV) genes. We previously developed an algorithm for quantifying the graphical properties of IGV gene lineage trees, allowing evaluation of the dynamical interplay between SHM and antigen-driven selection in different lymphoid tissues, species, and disease situations. Here, we apply this method to ectopic GC B cell clones from patients with Myasthenia Gravis, Rheumatoid Arthritis, and Sjögren’s Syndrome, using data scaling to minimize the effects of the large variability due to methodological differences between groups. Autoimmune trees were found to be significantly larger relative to normal controls. In contrast, comparison of the measurements for tree branching indicated that similar selection pressure operates on autoimmune and normal control clones

Evaluation of Trace Alignment Quality and its Application in Medical Process Mining

Trace alignment algorithms have been used in process mining for discovering the consensus treatment procedures and process deviations. Different alignment algorithms, however, may produce very different results. No widely-adopted method exists for evaluating the results of trace alignment. Existing reference-free evaluation methods cannot adequately and comprehensively assess the alignment quality. We analyzed and compared the existing evaluation methods, identifying their limitations, and introduced improvements in two reference-free evaluation methods. Our approach assesses the alignment result globally instead of locally, and therefore helps the algorithm to optimize overall alignment quality. We also introduced a novel metric to measure the alignment complexity, which can be used as a constraint on alignment algorithm optimization. We tested our evaluation methods on a trauma resuscitation dataset and provided the medical explanation of the activities and patterns identified as deviations using our proposed evaluation methods.Comment: 10 pages, 6 figures and 5 table

The effects of winglets on low aspect ratio wings at supersonic Mach numbers

A computational study was conducted on two wings, of aspect ratios 1.244 and 1.865, each having 65 degree leading edge sweep angles, to determine the effects of nonplanar winglets at supersonic Mach numbers. A Mach number of 1.62 was selected as the design value. The winglets studied were parametrically varied in alignment, length, sweep, camber, thickness, and dihedral angle to determine which geometry had the best predicted performance. For the computational analysis, an available Euler marching technique was used. The results indicated that the possibility existed for wing-winglet geometries to equal the performance of wing-alone bodies in supersonic flows with both bodies having the same semispan. The first wing with winglet used NACA 1402 airfoils for the base wing and was shown to have lift-to-pressure drag ratios within 0.136 percent to 0.360 percent of the NACA 1402 wing-alone. The other base wing was a natural flow wing which was previously designed specifically for a Mach number of 1.62. The results obtained showed that the natural wing-alone had a slightly higher lift-to-pressure drag than the natural wing with winglets

Efficient seeding techniques for protein similarity search

We apply the concept of subset seeds proposed in [1] to similarity search in protein sequences. The main question studied is the design of efficient seed alphabets to construct seeds with optimal sensitivity/selectivity trade-offs. We propose several different design methods and use them to construct several alphabets.We then perform an analysis of seeds built over those alphabet and compare them with the standard Blastp seeding method [2,3], as well as with the family of vector seeds proposed in [4]. While the formalism of subset seed is less expressive (but less costly to implement) than the accumulative principle used in Blastp and vector seeds, our seeds show a similar or even better performance than Blastp on Bernoulli models of proteins compatible with the common BLOSUM62 matrix

Efficient seeding techniques for protein similarity search

We apply the concept of subset seeds proposed in [1] to similarity search in protein sequences. The main question studied is the design of efficient seed alphabets to construct seeds with optimal sensitivity/selectivity trade-offs. We propose several different design methods and use them to construct several alphabets.We then perform an analysis of seeds built over those alphabet and compare them with the standard Blastp seeding method [2,3], as well as with the family of vector seeds proposed in [4]. While the formalism of subset seed is less expressive (but less costly to implement) than the accumulative principle used in Blastp and vector seeds, our seeds show a similar or even better performance than Blastp on Bernoulli models of proteins compatible with the common BLOSUM62 matrix

Temporal and spatial expression of genes involved in DNA methylation during reproductive development of sexual and apomictic Eragrostis curvula

Recent reports in model plant species have highlighted a role for DNA methylation pathways in the regulation of the somatic-to-reproductive transition in the ovule, suggesting that apomixis (asexual reproduction through seeds) likely relies on RdDM downregulation. Our aim was therefore to explore this hypothesis by characterizing genes involved in DNA methylation in the apomictic grass Eragrostis curvula. We explored floral transcriptomes to identify homologs of three candidate genes, for which mutations in Arabidopsis and maize mimic apomixis (AtAGO9/ZmAGO104, AtCMT3/ZmDMT102/ZmDMT105, and AtDDM1/ZmCHR106), and compared both their spatial and temporal expression patterns during reproduction in sexual and apomictic genotypes. Quantitative expression analyses revealed contrasting expression patterns for the three genes in apomictic vs sexual plants. In situ hybridization corroborated these results for two candidates, EcAGO104 and EcDMT102, and revealed an unexpected ectopic pattern for the AGO gene during germ line differentiation in apomicts. Although our data partially support previous results obtained in sexual plant models, they suggest that rather than an RdDM breakdown in the ovule, altered localization of AtAGO9/ZmAGO104 expression is required for achieving diplospory in E. curvula. The differences in the RdDM machinery acquired during plant evolution might have promoted the emergence of the numerous apomictic paths observed in plants.Fil: Selva, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Centro de Recursos Naturales Renovables de la Zona Semiárida. Universidad Nacional del Sur. Centro de Recursos Naturales Renovables de la Zona Semiárida; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Siena, Lorena Adelina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Investigaciones en Ciencias Agrarias de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Agrarias. Instituto de Investigaciones en Ciencias Agrarias de Rosario; ArgentinaFil: Rodrigo, Juan Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Centro de Recursos Naturales Renovables de la Zona Semiárida. Universidad Nacional del Sur. Centro de Recursos Naturales Renovables de la Zona Semiárida; Argentina. Universidad Nacional del Sur. Departamento de Agronomía; ArgentinaFil: Garbus, Ingrid. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Centro de Recursos Naturales Renovables de la Zona Semiárida. Universidad Nacional del Sur. Centro de Recursos Naturales Renovables de la Zona Semiárida; Argentina. Universidad Nacional del Sur. Departamento de Ciencias de la Salud; ArgentinaFil: Zappacosta, Diego Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Centro de Recursos Naturales Renovables de la Zona Semiárida. Universidad Nacional del Sur. Centro de Recursos Naturales Renovables de la Zona Semiárida; Argentina. Universidad Nacional del Sur. Departamento de Agronomía; ArgentinaFil: Romero, José Rodolfo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Centro de Recursos Naturales Renovables de la Zona Semiárida. Universidad Nacional del Sur. Centro de Recursos Naturales Renovables de la Zona Semiárida; ArgentinaFil: Ortiz, Juan Pablo Amelio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Investigaciones en Ciencias Agrarias de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Agrarias. Instituto de Investigaciones en Ciencias Agrarias de Rosario; ArgentinaFil: Pessino, Silvina Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Investigaciones en Ciencias Agrarias de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Agrarias. Instituto de Investigaciones en Ciencias Agrarias de Rosario; ArgentinaFil: Leblanc, O.. Universidad de Montpellier; AlemaniaFil: Echenique, Carmen Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Centro de Recursos Naturales Renovables de la Zona Semiárida. Universidad Nacional del Sur. Centro de Recursos Naturales Renovables de la Zona Semiárida; Argentina. Universidad Nacional del Sur. Departamento de Agronomía; Argentin