Bioinformatics Study On Transcriptome Of Human Fetal Liver Aged 22 Weeks Of Gestation And Genome Of SARS-CoV(JB-01)

Bioinformatics Study on Transcriptome of Human Fetal Liver Aged 22 Weeks ofGestationBackgrounds: Human fetal liver aged 22 wk of gestation (HFL22w), consistes of hepatic parenchyma cells and hematopoietic stem/progenitor cells, and corresponds to the turning point between immigration and emigration of the hematopoietic system. We had studied HFL22w before, but with improvements of data sources including: (1) The rapid growth of expressed sequence tags (ESTs) in dbEST; (2) The renewal of the GenBank non-redundant database; (3)The establishment of Gene Ontology (GO); (4) The increase of tissues expression profiling data coming from microarray; (5) The continuous perfection of UniGene, DoTs, MGC and Twinscan program, we must study on HFL22w once more, for the purpose of protein identification in proteomics, protein-protein interaction network research, and new gene function study.Aims: (1) Clustering of EST to get EST frequency information, and identifying gene; (2) GO classification for known genes to build standard expression profiling about HFL22w and to compare with those of other tissues; (3) validation of the results to get predicted proteins and their functional informations from unknown ESTs.Methods: The ESTs were first searched against the GenBank non-redundant database, UniGene, DoTs, MGC and Twinscan database for the identification of gene and a more perfected clustering of the ESTs. After classifying those known ESTs by using GO, those unknown ESTs were assembled by using PHRAP, then validated, and obtained full length ORF database of HFL22w. The encoding proteins were studied to get their function information. Finally, the known ESTs profile was compared with five tissues expression profile from the microarray data.Results: There are 16674 ESTs sequenced from a 3'-directed cDNA library of HFL22w. Among them, 8097 (48.6%) (Group I) matched to known genes or had partial homology to knowngenes; 4271 (25.6%) (Group II) exhibited no significant homology to known genes; and the remaining 4306 (25.8%) (Group III) were genomic sequences of unknown function, mitochondrial genomic sequences, bacterial DNA and repetitive sequences. The 2483 genes corresponding to Group I can be divided into 425 gene categories by GO classification. Some of the genes are related to metabolism, biosynthesis, development, cell proliferation, defense response, cell migration, hemopoiesis and endocytosis. The correlation coefficient (0.994) between the Group I and fetal liver data from microarray indicates their high similarity. Comparison on microarray data of five tissues (including fetal liver, bone marrow, liver, thymus and lymph node) indicates that genes related to reproduction, coagulation, homeostasis, regulation of gene expression (epigenetic), biosynthesis, energy pathways, cell migration, response to pathogenic bacteria, and natural killer cell mediated cytolysis in fetal liver are more than in other four tissues. Hierarchical clustering of these tissues shows that thymus and lymph node are closely related, thymus and bone marrow, liver and fetal liver are the next, fetal liver and bone marrow are the last. 2416 genes corresponding to Group II were assembled and their average length was lengthened from 342 bp to 1682 bp. 2098 genes (86.84%) of unknown ESTs had been prolonged. In these 2098 genes, 1037 genes (49.43%) were validated by UniGene, DoTs, MGC and Twinscan database. Then we predicted the characteristics of proteins (1921 genes) with length not less than 30 aa and obtained 277 profiles or patterns. More than 10 types were discussed.Conclusions: (1) The results of ESTs clustering show that the number of high expressed genes is small, but these genes include more ESTs than the others; (2) We obtained 1379 new genes; (3) GO analysis showed that human fetal liver display some typical characteristics of gene expression patterns related to special physiological functions; (4) Comparison of gene expression on five tissues showed that human fetal liver and liver have closer relation than the other tissues; (5) 1037 full length cDNAs and ORFs were obtained by assembling unknown ESTs and validation.Bioinformatics Study on Genome of SARS-CoV(BJ-Ol)SIGNIFICANCES: SARS, an atypical pneumonia of unknown aetiology, was recognized at the end of February 2003. For understanding the disease and cured it, we must got its gene informations.