Biomedical subjects

Xiaoqiu Huang

Publications and source records attributed to Xiaoqiu Huang.

13 recordsLinked to original sources

PubMed2006

Dynamic use of multiple parameter sets in sequence alignment.

The level of conservation between two homologous sequences often varies among sequence regions; functionally important domains are more conserved than the remaining regions. Thus, multiple parameter sets should be used in alignment of homologous sequences with a stringent parameter set for highly conserved regions and a moderate parameter set for weakly conserved regions. We describe an alignment algorithm to allow dynamic use of multiple parameter sets with different levels of stringency in computation of an optimal alignment of two sequences. The algorithm dynamically considers various candidate alignments, partitions each candidate alignment into sections, and determines the most appropriate set of parameter values for each section of the alignment. The algorithm and its local alignment version are implemented in a computer program named GAP4. The local alignment algorithm in GAP4, that in its predecessor GAP3, and an ordinary local alignment program SIM were evaluated on 257,716 pairs of homologous sequences from 100 protein families. On 168,475 of the 257,716 pairs (a rate of 65.4%), alignments from GAP4 were more statistically significant than alignments from GAP3 and SIM.

Algorithms↗

PubMed2006

Application of a superword array in genome assembly.

We introduce a data structure called a superword array for finding quickly matches between DNA sequences. The superword array possesses some desirable features of the lookup table and suffix array. We describe simple algorithms for constructing and using a superword array to find pairs of sequences that share a unique superword. The algorithms are implemented in a genome assembly program called PCAP.REP for computation of overlaps between reads. Experimental results produced by PCAP.REP and PCAP on a whole-genome dataset show that PCAP.REP produced a more accurate and contiguous assembly than PCAP.

Algorithms↗

PubMed2006

Physical map-assisted whole-genome shotgun sequence assemblies.

We describe a targeted approach to improve the contiguity of whole-genome shotgun sequence (WGS) assemblies at run-time, using information from Bacterial Artificial Chromosome (BAC)-based physical maps. Clone sizes and overlaps derived from clone fingerprints are used for the calculation of length constraints between any two BAC neighbors sharing 40% of their size. These constraints are used to promote the linkage and guide the arrangement of sequence contigs within a sequence scaffold at the layout phase of WGS assemblies. This process is facilitated by FASSI, a stand-alone application that calculates BAC end and BAC overlap length constraints from clone fingerprint map contigs created by the FPC package. FASSI is designed to work with the assembly tool PCAP, but its output can be formatted to work with other WGS assembly algorithms able to use length constraints for individual clones. The FASSI method is simple to implement, potentially cost-effective, and has resulted in the increase of scaffold contiguity for both the Drosophila melanogaster and Cryptococcus gattii genomes when compared to a control assembly without map-derived constraints. A 6.5-fold coverage draft DNA sequence of the Pan troglodytes (chimpanzee) genome was assembled using map-derived constraints and resulted in a 26.1% increase in scaffold contiguity.

Animals↗

PubMed2005

Evolution of alternative splicing after gene duplication.

Alternative splicing and gene duplication are two major sources of proteomic function diversity. Here, we study the evolutionary trend of alternative splicing after gene duplication by analyzing the alternative splicing differences between duplicate genes. We observed that duplicate genes have fewer alternative splice (AS) forms than single-copy genes, and that a negative correlation exists between the mean number of AS forms and the gene family size. Interestingly, we found that the loss of alternative splicing in duplicate genes may occur shortly after the gene duplication. These results support the subfunctionization model of alternative splicing in the early stage after gene duplication. Further analysis of the alternative splicing distribution in human duplicate pairs showed the asymmetric evolution of alternative splicing after gene duplications; i.e., the AS forms between duplicates may differ dramatically. We therefore conclude that alternative splicing and gene duplication may not evolve independently. In the early stage after gene duplication, young duplicates may take over a certain amount of protein function diversity that previously was carried out by the alternative splicing mechanism. In the late stage, the gain and loss of alternative splicing seem to be independent between duplicates.

Alternative Splicing↗

PubMed2005

A method for finding single-nucleotide polymorphisms with allele frequencies in sequences of deep coverage.

BACKGROUND: The allele frequencies of single-nucleotide polymorphisms (SNPs) are needed to select an optimal subset of common SNPs for use in association studies. Sequence-based methods for finding SNPs with allele frequencies may need to handle thousands of sequences from the same genome location (sequences of deep coverage). RESULTS: We describe a computational method for finding common SNPs with allele frequencies in single-pass sequences of deep coverage. The method enhances a widely used program named PolyBayes in several aspects. We present results from our method and PolyBayes on eighteen data sets of human expressed sequence tags (ESTs) with deep coverage. The results indicate that our method used almost all single-pass sequences in computation of the allele frequencies of SNPs. CONCLUSION: The new method is able to handle single-pass sequences of deep coverage efficiently. Our work shows that it is possible to analyze sequences of deep coverage by using pairwise alignments of the sequences with the finished genome sequence, instead of multiple sequence alignments.

Computers, Molecular↗

PubMed2005

MAP2: multiple alignment of syntenic genomic sequences.

We describe a multiple alignment program named MAP2 based on a generalized pairwise global alignment algorithm for handling long, different intergenic and intragenic regions in genomic sequences. The MAP2 program produces an ordered list of local multiple alignments of similar regions among sequences, where different regions between local alignments are indicated by reporting only similar regions. We propose two similarity measures for the evaluation of the performance of MAP2 and existing multiple alignment programs. Experimental results produced by MAP2 on four real sets of orthologous genomic sequences show that MAP2 rarely missed a block of transitively similar regions and that MAP2 never produced a block of regions that are not transitively similar. Experimental results by MAP2 on six simulated data sets show that MAP2 found the boundaries between similar and different regions precisely. This feature is useful for finding conserved functional elements in genomic sequences. The MAP2 program is freely available in source code form at http://bioinformatics.iastate.edu/aat/sas.html for academic use.

Algorithms↗

PubMed2004

Over 20% of human transcripts might form sense-antisense pairs.

The major challenge to identifying natural sense- antisense (SA) transcripts from public databases is how to determine the correct orientation for an expressed sequence, especially an expressed sequence tag sequence. In this study, we established a set of very stringent criteria to identify the correct orientation of each human transcript. We used these orientation-reliable transcripts to create 26 741 transcription clusters in the human genome. Our analysis shows that 22% (5880) of the human transcription clusters form SA pairs, higher than any previous estimates. Our orientation-specific RT-PCR results along with the comparison of experimental data from previous studies confirm that our SA data set is reliable. This study not only demonstrates that our criteria for the prediction of SA transcripts are efficient, but also provides additional convincing data to support the view that antisense transcription is quite pervasive in the human genome. In-depth analyses show that SA transcripts have some significant differences compared with other types of transcripts, with regard to chromosomal distribution and Gene Ontology-annotated categories of physiological roles, functions and spatial localizations of gene products.

Base Pairing↗

PubMed2004

Fibroblast growth and H-7 protein kinase inhibitor response monitored in microimpedance sensor arrays.

Functional genomic studies and drug candidate testing both require high throughput, parallel experimentation strategies to screen for variable cellular behaviors. In this article we describe the use of an impedance sensing electrode array that is capable of sensing cell "presence" as well as the extent of cell (focal) attachment to the substrate. The signals provided by mouse fibroblasts on a sensing structure containing four different sized electrodes are reported. In the absence of cells, each electrode's impedance was found to depend as expected on electrode size and frequency. The impedance increased by several-fold when fibroblasts attached and spread out over time. More notably, the sensors also detected the cellular response to the protein kinase C inhibitor, H-7. H-7 inhibits actomyosin contractility; thereafter, the loss of focal adhesion complexes occurs. The sensors, in turn, detected an impedance decrease after H-7 addition and an increase in impedance after H-7 removal.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed2004

Efficient combination of multiple word models for improved sequence comparison.

MOTIVATION: Studies of efficient and sensitive sequence comparison methods are driven by a need to find homologous regions of weak similarity between large genomes. RESULTS: We describe an improved method for finding similar regions between two sets of DNA sequences. The new method generalizes existing methods by locating word matches between sequences under two or more word models and extending word matches into high-scoring segment pairs (HSPs). The method is implemented as a computer program named DDS2. Experimental results show that DDS2 can find more HSPs by using several word models than by using one word model. AVAILABILITY: The DDS2 program is freely available for academic use in binary code form at http://bioinformatics.iastate.edu/aat/align/align.html and in source code form from the corresponding author.

Algorithms↗

PubMed2003

TIGR Gene Indices clustering tools (TGICL): a software system for fast clustering of large EST datasets.

TGICL is a pipeline for analysis of large Expressed Sequence Tags (EST) and mRNA databases in which the sequences are first clustered based on pairwise sequence similarity, and then assembled by individual clusters (optionally with quality values) to produce longer, more complete consensus sequences. The system can run on multi-CPU architectures including SMP and PVM.

Cluster Analysis↗

PubMed2003

A generalized global alignment algorithm.

MOTIVATION: Homologous sequences are sometimes similar over some regions but different over other regions. Homologous sequences have a much lower global similarity if the different regions are much longer than the similar regions. RESULTS: We present a generalized global alignment algorithm for comparing sequences with intermittent similarities, an ordered list of similar regions separated by different regions. A generalized global alignment model is defined to handle sequences with intermittent similarities. A dynamic programming algorithm is designed to compute an optimal general alignment in time proportional to the product of sequence lengths and in space proportional to the sum of sequence lengths. The algorithm is implemented as a computer program named GAP3 (Global Alignment Program Version 3). The generalized global alignment model is validated by experimental results produced with GAP3 on both DNA and protein sequences. The GAP3 program extends the ability of standard global alignment programs to recognize homologous sequences of lower similarity. AVAILABILITY: The GAP3 program is freely available for academic use at http://bioinformatics.iastate.edu/aat/align/align.html.

Algorithms↗

PubMed2003

MAVG: locating non-overlapping maximum average segments in a given sequence.

SUMMARY: MAVG is a software tool for finding k non-overlapping maximum-average segments that are sufficiently long in a given sequence of real numbers, for any k > 0. It has applications in several areas of biomolecular sequence analysis including locating GC-rich regions and CpG islands in a genomic sequence, and annotating multiple sequence alignments. AVAILABILITY: http://iubio.bio.indiana.edu/soft/molbio/pattern/cpg_islands/.

Algorithms↗

PubMed2003

PCAP: a whole-genome assembly program.

We describe a whole-genome assembly program named PCAP for processing tens of millions of reads. The PCAP program has several features to address efficiency and accuracy issues in assembly. Multiple processors are used to perform most time-consuming computations in assembly. A more sensitive method is used to avoid missing overlaps caused by sequencing errors. Repetitive regions of reads are detected on the basis of many overlaps with other reads, instead of many shorter word matches with other reads. Contaminated end regions of reads are identified and removed. Generation of a consensus sequence for a contig is based on an alignment of reads in the contig, in which both base quality values and coverage information are used to determine every consensus base. The PCAP program was tested on a mouse whole-genome data set of 30 million reads and a human Chromosome 20 data set of 1.7 million reads. The program is freely available for academic use.

Algorithms↗