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1.
J Immunol Methods ; : 113713, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38925438

RESUMO

MHC class I pathway consists of four main steps: proteasomal cleavage in the cytosol in which precursor proteins are cleaved into smaller peptides, which are then transported into the endoplasmic reticulum by the transporter associated with antigen processing, TAP, for further processing (trimming) from the N-terminal region by an ER resident aminopeptidases 1 (ERAP1) enzyme, to generate optimal peptides (8-10 amino acids in length) to produce a stable MHCI-peptide complex, that get transited via the Golgi apparatus to the cell surface for presentation to the cellular immune system. Several studies reported specificities related to the ERAP1 trimming process, yet there is no in silico tool for the prediction of the trimming process of the ERAP1 enzyme. In this paper, we provide and implement a prediction model for the trimming process of the ERAP1 enzyme.

2.
J Comput Biol ; 30(4): 538-551, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36999902

RESUMO

High-throughput DNA and RNA sequencing are revolutionizing precision oncology, enabling personalized therapies such as cancer vaccines designed to target tumor-specific neoepitopes generated by somatic mutations expressed in cancer cells. Identification of these neoepitopes from next-generation sequencing data of clinical samples remains challenging and requires the use of complex bioinformatics pipelines. In this paper, we present GeNeo, a bioinformatics toolbox for genomics-guided neoepitope prediction. GeNeo includes a comprehensive set of tools for somatic variant calling and filtering, variant validation, and neoepitope prediction and filtering. For ease of use, GeNeo tools can be accessed via web-based interfaces deployed on a Galaxy portal publicly accessible at https://neo.engr.uconn.edu/. A virtual machine image for running GeNeo locally is also available to academic users upon request.


Assuntos
Neoplasias , Humanos , Neoplasias/genética , Neoplasias/terapia , Medicina de Precisão , Genômica/métodos , Biologia Computacional , Imunoterapia , Sequenciamento de Nucleotídeos em Larga Escala
3.
J Comput Biol ; 24(4): 280-288, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27960065

RESUMO

Due to the significant amount of DNA data that are being generated by next-generation sequencing machines for genomes of lengths ranging from megabases to gigabases, there is an increasing need to compress such data to a less space and a faster transmission. Different implementations of Huffman encoding incorporating the characteristics of DNA sequences prove to better compress DNA data. These implementations center on the concepts of selecting frequent repeats so as to force a skewed Huffman tree, as well as the construction of multiple Huffman trees when encoding. The implementations demonstrate improvements on the compression ratios for five genomes with lengths ranging from 5 to 50 Mbp, compared with the standard Huffman tree algorithm. The research hence suggests an improvement on all such DNA sequence compression algorithms that use the conventional Huffman encoding. The research suggests an improvement on all DNA sequence compression algorithms that use the conventional Huffman encoding. Accompanying software is publicly available (AL-Okaily, 2016 ).


Assuntos
Algoritmos , Compressão de Dados/métodos , Análise de Sequência de DNA/métodos , Genômica , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Software
4.
J Comput Biol ; 23(7): 615-23, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27152692

RESUMO

Motif finding is an important and a challenging problem in many biological applications such as discovering promoters, enhancers, locus control regions, transcription factors, and more. The (l, d)-planted motif search, PMS, is one of several variations of the problem. In this problem, there are n given sequences over alphabets of size [Formula: see text], each of length m, and two given integers l and d. The problem is to find a motif m of length l, where in each sequence there is at least an l-mer at a Hamming distance of [Formula: see text] of m. In this article, we propose ET-Motif, an algorithm that can solve the PMS problem in [Formula: see text] time and [Formula: see text] space. The time bound can be further reduced by a factor of m with [Formula: see text] space. In case the suffix tree that is built for the input sequences is balanced, the problem can be solved in [Formula: see text] time and [Formula: see text] space. Similarly, the time bound can be reduced by a factor of m using [Formula: see text] space. Moreover, the variations of the problem, namely the edit distance PMS and edited PMS (Quorum), can be solved using ET-Motif with simple modifications but upper bands of space and time. For edit distance PMS, the time and space bounds will be increased by [Formula: see text], while for edited PMS the increase will be of [Formula: see text] in the time bound.


Assuntos
Análise de Sequência de DNA/métodos , Algoritmos , Biologia Computacional/métodos
5.
BMC Genomics ; 17: 193, 2016 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-26945881

RESUMO

BACKGROUND: Current high-throughput sequencing technologies generate large numbers of relatively short and error-prone reads, making the de novo assembly problem challenging. Although high quality assemblies can be obtained by assembling multiple paired-end libraries with both short and long insert sizes, the latter are costly to generate. Recently, GAGE-B study showed that a remarkably good assembly quality can be obtained for bacterial genomes by state-of-the-art assemblers run on a single short-insert library with very high coverage. RESULTS: In this paper, we introduce a novel hierarchical genome assembly (HGA) methodology that takes further advantage of such very high coverage by independently assembling disjoint subsets of reads, combining assemblies of the subsets, and finally re-assembling the combined contigs along with the original reads. CONCLUSIONS: We empirically evaluated this methodology for 8 leading assemblers using 7 GAGE-B bacterial datasets consisting of 100 bp Illumina HiSeq and 250 bp Illumina MiSeq reads, with coverage ranging from 100x- ∼200x. The results show that for all evaluated datasets and using most evaluated assemblers (that were used to assemble the disjoint subsets), HGA leads to a significant improvement in the quality of the assembly based on N50 and corrected N50 metrics.


Assuntos
Genoma Bacteriano , Genômica/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Mapeamento de Sequências Contíguas , Biblioteca Gênica , Análise de Sequência de DNA/métodos , Software
6.
J Comput Biol ; 22(12): 1118-28, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26402070

RESUMO

Approximate pattern matching is a fundamental problem in the bioinformatics and information retrieval applications. The problem involves different matching relations such as Hamming distance, edit distances, and the wildcards matching problem. The input is usually a text of length n over a fixed alphabet of length Σ, a pattern of length m, and an integer k. The output is to find all positions that have ≤ k Hamming distance, edit distance, or wildcards matching with P. Many algorithms and indexes have been proposed to solve the problems more efficiently, but due to the space and time complexities of the problems, most tools adopted heuristics approaches based on, for instance, suffix tree, suffix array, or Burrows Wheeler Transform to reach practical implementations. Error Tree is a novel tree structure that is mainly oriented to solve the approximate pattern matching problems, using less space and faster computation time. The algorithm proposes for Hamming distance and wildcards matching a tree structure that needs [Formula: see text] words and takes [Formula: see text] in the average case) of query time for any online/offline pattern, where occ is the number of outputs. In addition, a tree structure of [Formula: see text] words and [Formula: see text] in the average case) query time for edit distance for any online/offline pattern.


Assuntos
Indexação e Redação de Resumos/métodos , Biologia Computacional/métodos , Mineração de Dados/métodos , Software
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