Revealing the missing expressed genes beyond the human reference genome by RNA-Seq

Area of Science:

• Genomics
• Transcriptomics
• Bioinformatics

Background:

• A complete human reference genome is vital for functional genomics.
• Incomplete reference genomes and individual-specific sequences impact research accuracy.

Purpose of the Study:

• To investigate the completeness of the human reference genome using RNA-Seq data.
• To identify transcribed sequences and genes absent from current human genome builds.

Main Methods:

• Analysis of RNA-Seq datasets from human brain tissues and cell lines.
• Comparison of transcriptomic data against human reference genome builds (NCBI build 36 and 37).
• Identification and validation of novel transcribed sequences and conserved genes.

Main Results:

• Significant portions of novel sequences, previously absent from the reference genome, are transcribed.
• Numerous RefSeq genes unalignable to NCBI build 37 show expression in human tissues and cell lines.
• Hundreds of novel transcript contigs, some conserved across species, were identified, revealing large deletions in the reference genome.

Conclusions:

• The human reference genome remains incomplete, with many functional genes missing.
• Further refinement of the human reference genome and curation of missing genes are essential.
• Transcriptome-based comparative genomics offers a valuable approach for improving the human reference genome.