CancerTelSys | TelNet | Construction of TelNet

Construction of TelNet

User interface

The TelNet database is free to use without any login. TelNet is a searchable and user-friendly gene database that has the aim of providing a comprehensive platform to study genes that are involved in telomere maintenance mechanisms (TMM). The TelNet database itself has a mostly self-explanatory menu. On the start page we provide an overview on the database content for the two organisms H. sapiens and S. cerevisiae. The User can select an organism and choose between a card view for every individual record and a scrollable list view that shows selected fields for each gene entry. The navigation menu can be found on the top left. Each gene card consists of various fields containing annotations from external databases and peer-reviewed literature. General fields comprise the gene symbol, synonyms, a broad/detailed description and the most prominent cellular function. Frequently used identifiers for genes, transcripts and proteins were selected for each individual organism and linked to the respective external database. In the TM we provide specific information on the TM information of the gene, transcript or protein with telomere maintenance. Genes are also categorized according to their TM significance and the TelNet score is calculated. Organisms are connected via database hyperlinks next to the homologue fields. Literature information is listed and linked for every single gene. A short explanation is given by clicking on the little (i) buttons next to a field.

External databases

It is important to use standardized nomenclature (16) therefore the ID converter system from DAVID Bioinformatics Resources and gene information data from National Center for Biotechnology Information, NCBI was used to convert data retrieved from literature to get desired information on the approved gene symbol, full name, synonyms, gene description as well as often used identifiers such as Hugo Gene ID, Ensembl ID, Locus Tag, Refseq IDs of all isoforms and Uniprot ID. Especially for homologous search we used YeastMine from the Saccharomyces Genome Database, SGD, to retrieve the gene symbols of orthologous in human and yeast. Based on the functional annotations from Gene Ontology, GO we generated a list of cellular functions that can be entered in the respective field "cellular function".

Source of TMM genes

In the literature section we provide the source of TMM information which is cited and linked respectively. Here we categorize peer-reviewed literature into the three sections "validated by", "screened by" and "predicted by". According to the type of study the gene is found or investigated we assign a TM significance that has basically the same categories: "validated", "screened" and "predicted". If a gene's connection to TM is examined in more detail by an independent research article this source is cited and linked in the literature section 'validated by'. Also the TM significance of this record is then set to 'validated'.

To establish a solid foundation, at first gene lists from relevant screening studies or reviews in human or yeast have been selected that provide information on the role of a given protein involved in telomere maintenance.

While analyses like genome-wide deletion studies are challenging in human, however, the human orthologue is included in the TelNet database if a yeast gene's TM significance is categorized as 'screened' or 'validated'. This information is then provided in the literature section "predicted by". According to this procedure also yeast genes are included if the respective human orthologue shows a TM significance higher than 'predicted'.

H. sapiens (human)

Dejardin, J., Kingston, R.E. (2009) Purification of proteins associated with specific genomic Loci. Cell, 136, 175-186.

Grolimund, L., Aeby, E., Hamelin, R., et al. (2013) A quantitative telomeric chromatin isolation protocol identifies different telomeric states. Nat Commun, 4, 2848.

Lee, O.H., Kim, H., He, Q., et al. (2011) Genome-wide YFP fluorescence complementation screen identifies new regulators for telomere signaling in human cells. Mol Cell Proteomics, 10, M110 001628.

Osterwald, S., Deeg, K.I., Chung, I., et al. (2015) PML induces compaction, TRF2 depletion and DNA damage signaling at telomeres and promotes their alternative lengthening. J Cell Sci, 128, 1887-1900.

Uziel, O., Yosef, N., Sharan, R., et al. (2015) The effects of telomere shortening on cancer cells: a network model of proteomic and microRNA analysis. Genomics, 105, 5-16.

Ramlee, M.K., Wang, J., Toh, W.X., et al. (2016) Transcription Regulation of the Human Telomerase Reverse Transcriptase (hTERT) Gene. Genes (Basel), 7.

Cerone, M.A., Burgess, D.J., Naceur-Lombardelli, C., et al. (2011) High-Throughput RNAi Screening Reveals Novel Regulators of Telomerase. Cancer research, 71, 3328-3340.

Lovejoy, C.A., Li, W., Reisenweber, S., et al. (2012) Loss of ATRX, genome instability, and an altered DNA damage response are hallmarks of the alternative lengthening of telomeres pathway. PLoS Genet, 8, e1002772.

S. cerevisiae (budding yeast)

Ungar, L., Yosef, N., Sela, Y., et al. (2009) A genome-wide screen for essential yeast genes that affect telomere length maintenance. Nucleic Acids Research, 37, 3840-3849.

Askree, S.H., Yehuda, T., Smolikov, S., et al. (2004) A genome-wide screen for Saccharomyces cerevisiae deletion mutants that affect telomere length. Proceedings of the National Academy of Sciences of the United States of America, 101, 8658-8663.

Gatbonton, T., Imbesi, M., Nelson, M., et al. (2006) Telomere length as a quantitative trait: genome-wide survey and genetic mapping of telomere length-control genes in yeast. PLoS Genet, 2, e35.