In-silico human genomics with GeneCards

Abstract

Since 1998, the bioinformatics, systems biology, genomics and medical communities have enjoyed a synergistic relationship with the GeneCards database of human genes (http://www.genecards.org). This human gene compendium was created to help to introduce order into the increasing chaos of information flow. As a consequence of viewing details and deep links related to specific genes, users have often requested enhanced capabilities, such that, over time, GeneCards has blossomed into a suite of tools (including GeneDecks, GeneALaCart, GeneLoc, GeneNote and GeneAnnot) for a variety of analyses of both single human genes and sets thereof. In this paper, we focus on inhouse and external research activities which have been enabled, enhanced, complemented and, in some cases, motivated by GeneCards. In turn, such interactions have often inspired and propelled improvements in GeneCards. We describe here the evolution and architecture of this project, including examples of synergistic applications in diverse areas such as synthetic lethality in cancer, the annotation of genetic variations in disease, omics integration in a systems biology approach to kidney disease, and bioinformatics tools.

NAF-1 and mitoNEET are central to human breast cancer proliferation by maintaining mitochondrial homeostasis and promoting tumor growth

“…1A). These findings are supported by mRNA expression studies of NEET proteins in breast cancer cells (23)(24)(25), and suggest a role for NEET proteins in promoting mitochondrial biogenesis and autophagy resistance in cancer cells (23).…”

“…Interestingly, levels of mNT and NAF-1 mRNA are increased significantly in many different human cancer cells (23)(24)(25). The involvement of NAF-1 and mNT in mitochondrial metabolism and homeostasis, as well as in autophagy regulation, points to a possible role for these proteins in cell transformation.…”

“…NAF-1 is also localized to the endoplasmic reticulum, where it interacts with BCL-2 and Beclin 1 to regulate autophagy and apoptosis (8-13). Deficiency in mNT causes the accumulation of iron and ROS in mitochondria of animal and plant cells, and deficiency in NAF-1 results in decreased mitochondrial function and stability, as well as activation of autophagy in mice and human cells (13-16, 20, 21).Interestingly, levels of mNT and NAF-1 mRNA are increased significantly in many different human cancer cells (23)(24)(25). The involvement of NAF-1 and mNT in mitochondrial metabolism and homeostasis, as well as in autophagy regulation, points to a possible role for these proteins in cell transformation.…”

A genetic database can be utilized to identify potential biomarkers for biphenotypic hepatocellular carcinoma-cholangiocarcinoma

“…Prior studies have validated the use of this database in the study of several medical conditions (27)(28)(29)(30)(31)(32)(33). Specifically, this compendium has assisted researchers in identifying genes vital to the prognosis and pathogenesis of multiple malignancies, as well as non-neoplastic liver diseases (30)(31)(32)(33).…”

“…To evaluate the genetic associations with each variable we utilized GeneCards ® , The Human Gene Compendium (http://www.genecards.org) (27)(28)(29)(30)(31)(32)(33). Our initial search was performed on HCC alone, CC alone, and finally HCC-CC.…”