Identification of liver specific genes using next generation sequencing technology

Introduction: The next generation sequencing technology offers an entirely new perspective for clinical research and will speed up personalized medicine. In this work this new technology was used to identify a gene profile highly specific for healthy liver tissues, which could deal as a diagnostic tool to distinguish between a healthy or diseased liver.Material and Methods: Initially next generation sequencing data were downloaded from EMBL (ENA ERP000257). This genome-wide expression compendium originates from eleven, healthy, human tissue samples pooled from multiple donors. The tissues are as followed: adipose, colon, heart, hypothalamus, kidney, lung, ovary, skeletalmuscle, spleen, testes and liver. The expression level were estimated by mapping and counting reads to single gene sequences derived from the UCSC genome browser. To make the expression levels comparable across tissues the RPKM normalization was applied. Finally, genes were defined as liver specific if its liver RPKM is equal or greater than 10 and the reference tissues RPKMs are less or equal than 2. Results: A profile of 98 genes was identified, which meet the criteria for a specific liver gene. With 518 RPKMs the gene complement component 9 ranks on top of the list. Followed by ORM1, TAT; HPX and CPS1 and ITIH2 with 395, 205, 249, 311 and 171 RPKMs respectly. Investigation on pathway and functional levels revealed significant associations to lipid metabolism, molecular transport, coagulation systems as well as acute phase response signaling. Conclusion: Next generation sequencing identified a gene profile of 98 genes highly specific to healthy liver tissues, which shows significant associations to normal liver functions. Thereby this gene profile demonstrates the state of a healthy liver and thus, upon further validation, this gene profile could deal as a robust diagnostic tool to test for normal or pathological liver behavior.

bioinformatics - expression profiling - next generation sequencing