Gene Function Prediction

Frank & Birgit EISENHABER
Senior Principal Investigators

Swati SINHA, Fernanda SIROTA (part-time)
Post Doc Research Fellows

Lim Chun Teck
Senior Research Officer

Scientifically, the Gene Function Prediction group is focused on the prediction of molecular and cellular functions of genes and proteins based on the theoretical analysis of biomolecular sequences, expression profiles and other omics high-throughput data. Most of the work is with external collaborators, also including partners in clinics and biotech/pharma industry. Besides that, this group also provides support for teams in BII, an organizational fallback for staff involved in various collaborations, software development and incubation activities that do not readily fit into other existing PI-led teams.

Dramatic recent improvements of nucleic acid sequencing technologies enhance the prospect of general availability of genomes from patients, patient-specific pathogens and of gene expression data. This development has profound implications for life science research and biomedical applications. Sequencing is becoming the single most informative research technology in life sciences; consequently, sequence analysis and sequence-based structure and function prediction will be more important than ever.

This team invests and will continue with great effort in maintaining and developing tools for biomolecular sequence studies and functional assessments as well as their application in biological/medical projects (in collaboration with I. Berezovsky, S. Maurer-Stroh and Wong W.-C., BII). A description of the ANNOTATOR software suite with additional features (functional loop identification, transmembrane complexity detection, etc.) has been published. A new tool for superfast large-scale domain annotation, xHMMER3x2, has been developed.

Sequence analytic applications cover (i) the exploration of allosteric modulation of the catalytic activity of the Insulin-Degrading Enzyme (IDE) against amyloid peptides based on single-residue mutations, (ii) the genome-wide comparative analysis of codon usage bias and codon context patterns among cyanobacterial genomes, (iii) the prediction of viral proteins to be prenylated by enzymes of the host organism as a basis for a virus-driven rationale for therapy with statins and FT/GGT1 inhibitors, (iv) the analysis of gene networks in influenza virus – human host interactions. We discovered a "non-negative-inside/negative outside" (NNI/NO-) rule that complements the positive-inside rule in the flanks of transmembrane regions in membrane proteins.

Studies of proteins' post-translational modifications and translocation signals have been a main topic for this team. It was found that, in the case of FCAR isoforms, the efficiency of signal peptides depends on the type of the following sequence region/domain. PIG-U (a subunit of the GPI lipid anchor transamidase complex) dis-regulation in papillary thyroid carcinoma is linked to the efficiency of radioactive iodine therapy.

The collaboration with the G. Grüber crystallography lab (NTU, Singapore) resulted in a string of discoveries with regard to the structure, catalytic mechanism and sequence architecture significance of the AhpF/AhpC alkylhydroperoxide reductase complex by studies of mutated versions of AhpF/AhpC. Circular permutation was found to be a feature of the AhpF protein family as demonstrated for the Enterococcus faecalis (V583) AhpF protein.

The team continues to be successful in attracting grants and industry collaborations (BE: IMaGIN, the computational biology component of A*STAR's "Biomass-to-Chemicals" program, BE: NRF-CRP17-2017-03 (green and sustainable pharmaceutical manufacturing via biocatalysis), FE:Cat3 “Integrated Genomics Platform”, FE: ATTRAcT clinical data analysis for heart failure patients). The team is involved in industry-funded projects in collaboration with the BII Natural Organism Library.

Figure 1
Figure 1: Residue distributions of transmembrane anchors. A view showing additional residue distribution features that TMHs with an anchorage function display.
A) The more classic model of a TMH showing the "positive-inside" rule, the hydrophobic core, the polar enrichment that flanks the hydrophobic stretch and the aromatic belt.
B) Simple anchors may display additional features that conform to the membrane biophysical constraints: further suppression of charge in the hydrophobic core, intra-membrane leucine asymmetry that likely causes hydrophobic skew, a higher preference for cysteine on the inside flanking region, a higher net "positiveinside" charge, asymmetric skew of the hydrophobic belt favoring the inner leaflet interface and a negative-outside bias via suppression on the inside flanking region or enrichment on the outside flanking region.

Gene Function Prediction Group Members

Dr. EISENHABER Frank
Head of Division
 
  Biography Details
Dr. EISENHABER Birgit
Principal Investigator
 
  Biography Details
NameTitle
Dr. EISENHABER FrankPrincipal Investigator
Dr. EISENHABER Birgit Principal Investigator
Dr. SINHA SwatiPostdoctoral Fellow
Dr. SIROTA Fernanda L.Postdoctoral Fellow
Mr. LIM Chun TeckResearch Officer

This section is still work in progress.