Gene finding remains an important problem in biology as scientists are still far from fully mapping the set of human genes. Furthermore, gene maps for other vertebrates, including important model organisms such as mouse, are much more incomplete than the human annotation. The new technique, known as CONTRAST (CONditionally TRAined Search for Transcripts), works by comparing a genome of interest to the genomes of several related species.
CONTRAST exploits the fact that the functional role protein-coding genes play a specific part within a cell and are therefore subjected to characteristic evolutionary pressures. For example, mutations that alter an important part of a protein's structure are likely to be deleterious and thus selected against. On the other hand, mutations that preserve a protein's amino acid sequence are normally well tolerated. Thus, protein-coding genes can be identified by searching a genome for regions that show evidence such patterns of selection. However, learning to recognize such patterns when more than two species are compared has proved difficult.
Previous systems for gene prediction were able to effectively make use of one additional 'informant' genome. For example, when searching for human genes, taking into account information from the mouse genome led to a substantial increase in accuracy. But, no system was able to leverage additional informant genomes to improve upon state-of-the-art performance using mouse alone, although it was expected that adding informants would make patterns of selection clearer. CONTRAST solves this problem by learning to recognize the signature of protein-coding gene selection in a fundamentally different way from previous approaches. Instead of constructing a model of sequence evolution, CONTRAST directly 'learns' which features of a genomic alignment are most useful for recognizing genes. This approach leads to overall higher levels of accuracy and is able to extract useful information from several informant sequences.
In a test on the human genome, CONTRAST exactly predicted the full structure of 59% of the genes in the test set, compared with the previous best result of 36%. Its exact exon sensitivity of 93%, compared with a previous best of 84%, translates into many thousands of exons correctly predicted by CONTRAST but missed by previous methods. Importantly, CONTRAST's accuracy using a combination of eleven informant genomes was significantly higher than its accuracy using any single informant. The substantial advance in predictive accuracy represented by CONTRAST will further efforts to complete protein-coding gene maps for human and other organisms.
Further information about existing gene-prediction methods and the advance CONTRAST brings to the field can be found in a minireview by Paul Flicek, which accompanies the article by Batzoglou and colleagues.
One step closer to reality
20.04.2018 | Max-Planck-Institut für Entwicklungsbiologie
The dark side of cichlid fish: from cannibal to caregiver
20.04.2018 | Veterinärmedizinische Universität Wien
University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.
Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.
Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.
Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...
Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.
The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...
Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.
Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...
In the fight against cancer, scientists are developing new drugs to hit tumor cells at so far unused weak points. Such a “sore spot” is the protein complex...
13.04.2018 | Event News
12.04.2018 | Event News
09.04.2018 | Event News
20.04.2018 | Health and Medicine
20.04.2018 | Materials Sciences
20.04.2018 | Earth Sciences