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Table of contents
1 introduction
1.1 Overview of the study
ii background and problem statement
2 studying immune repertoires
2.1 An overview of the human adaptive immune system
2.2 Generation and maturation of lymphocytes
2.3 Basic structure of B cell receptor
2.4 The practical aspects of measuring BCR repertoire’s diversity
2.4.1 The sample size
2.4.2 The capacity of current sequencing instruments
3 bioinformatics pipelines and repertoire analysis
3.1 Pre-processing
3.2 Sequence analysis and clustering clonally related sequences
3.2.1 VDJ germline assignment
3.2.2 Clonal grouping
3.3 Repertoire characterization and analysis
3.3.1 Diversity Profiles
3.3.2 Mutation analysis
3.3.3 Clonal Evolution / Evolution of repertoire /clonal dynamic
4 the definition of clone
5 a communication model for optimizing rep-seq clinical use
6 the problem statement
iii proposed solutions
7 agreeable; a bcr repertoire clonal grouping method with an application for intra-clonal analysis in clinical settings
7.1 Introduction
7.2 Material and Methods
7.2.1 The algorithm
7.2.2 Data sets
7.2.3 Performance evaluation
7.3 Results
7.3.1 Reconstruction simulated repertoire’s clonal architecture
7.3.2 Parameter optimization
7.3.3 Runtime
7.3.4 Outputs’ interpretability
7.3.5 Usability
7.4 Discussion
8 performance evaluation of bcr clonal grouping algorithms
8.1 Introduction
8.2 Material and Methods
8.2.1 Clonal grouping methods
8.2.2 BCR high throughput sequencing data
8.2.3 Performance evaluation
8.3 Results
8.3.1 Simulated repertoires
8.3.2 Artificial monoclonal repertoires
8.3.3 Experimental benchmarks
8.4 Discussion
9 reconstructing the evolutionary history of a bcr lineage using minimum spanning tree and clonotype abundances
9.1 Introduction
9.2 Material and methods
9.2.1 Problem statement
9.2.2 Minimum spanning Tree
9.2.3 A modified Prim’s algorithm
9.2.4 Editing the reconstructed lineage tree
9.2.5 Tools used in the comparisons
9.2.6 Data sets
9.2.7 Tree comparison and evaluation
9.3 Results
9.3.1 Reconstructing BCR lineage trees from simulated data
9.3.2 Biological validation using BCR sequencing data
9.4 Discussion
10 viclod, a tool for visualizing b cell repertoire’s clonal and intra-clonal diversities
10.1 Pipeline
10.2 Description of functionalities
10.2.1 Clonal analysis
10.2.2 Intra-clonal diversity analysis
10.2.3 Pruning trees for a better interpretation
10.2.4 Intra-clonal diversity analysis
10.2.5 Availability
10.2.6 Implementation
10.2.7 Downloads
10.3 Use case
10.4 Conclusion
iv conclusion and perspectives
11 conclusion and perspectives
11.0.1 Conclusion
11.0.2 Direction for future work
v appendix
a airr file’s required fields for viclod pipeline
b comparison of bcr clonal grouping tools’ performance
on simulated repertoires
bibliography



