[Frontiers in Bioscience 2, a31-36, November 1, 1997]
Reprints
PubMed
CAVEAT LECTOR




Table of Conents
 Previous Section   Next Section

FUNCTIONAL BIOINFORMATICS: THE CELLULAR RESPONSE DATABASE

James Sorace1,2,3, Kip Canfield1, Steven Russell1

1 Department of Information Systems, University of Maryland Baltimore County, 2The Department of Pathology and Laboratory Service Baltimore VA Medical Center, 3 Department of Pathology, University of Maryland at Baltimore School of Medicine, Baltimore, Maryland

Received 4/3/97 Accepted 10/24/97

4. RESULTS OF TRIAL QUERIES

In order to demonstrate the utility of the data model, data from several of the thalidomide references noted above (1,2), and from a set of studies describing a family of interferon (IFN) induced GTPase like molecules (8,9,10), have been entered into the prototype CRD. The GTPase family currently consists of four published sequences, which show significant sequence homology with one another (8,9,10,11,12). Their expression is known to be modulated by a wide variety of agents including LPS, and IFNs. For some members of this family, patterns of inhibition or lack of induction by cytokines or drugs have also been reported. Based on these data, we have developed several queries that include:

1. Find the pattern(s) of response and manuscript reference for a given test agent. An example of this query, using thalidomide as the test agent, is shown in table 3, Panel A. Source data can be found in figure 2 and table 1 of reference 1, and figure 2 of reference 2.

2. Find the target genes up regulated by a cytokine, and display the test cell population. An example of this query is shown in table 3. Panel B, for IFN-gamma. Source data may be found in the first figure of references 8,9 and 10.

3. Find conditions in which an agent down-regulates the expression of a gene. The data from this query is shown in table 3, Panel C. This illustrates that LPS inhibits the ability of IFN-gamma to induce the MG21 GTPase. Source data may be found in figure 5 of reference 9.

4. List all other agents which have been assayed in combination with a given test agent. table 3, Panel D, lists all agents and assays that are linked to thalidomide as a test agent. Source data may be found in tables 1 and 2 of reference 1 (assay numbers 1-5, and 33), and figure 2A of reference 2 (assay number 6).

Table 3: Outputs of example queries*

PANEL A

Agent.Name

Gene_Protein.Name

Species

Pattern of Response

First Author

Journal

Volume

Page

Thalidomide

TNF-Alpha

Human

UP regulated, but present before stimulation

Makonkaweyoon S

Proc Natl Acad Sci, USA

90

5974

Thalidomide

HIV-1 Reverse Transcritptase Activity

Human

Down regulated

Makonkaweyoon S

Proc Natl Acad Sci, USA

90

5974

Thalidomide

TNF-Alpha

Human

Down regulated

Peterson PK

J Infect Dis

172

1137

Thalidomide

HIV-1 Reverse Transcritptase Activity

Human

Variable depending on conditions

Makonkaweyoon S

Proc Natl Acad Sci, USA

90

5974

PANEL B

Agent.Name

Agent Role

Assay_Counter

Cell_Name

Cell_Type

Gene_Protein.Name

IFN- gamma

TEST

14

RAW 264.7

Macrophage

LRG-47

IFN-gamma

TEST

20

BCL1

B-cell lymphoma

LRG-47

IFN-gamma

TEST

25

RAW 264.7

Macrophage

iGTP

IFN-gamma

TEST

28

RAW 264.7

Macrophage

iGTP

IFN-gamma

TEST

30

Peritoneal Cells

Macrophage

Mg21

IFN-gamma

TEST

31

Peritoneal Cells

Macrophage

Mg21

PANEL C

Agent.Name

Exposure

(hour)

Concentration

(microgram/ml)

Additional Agents

By Assay

Concentration

Units

LPS

6

10

IFN-gamma

1000

Units/ml

Gene_Protein.Name

Cell._Name

Cell_Type

Mg21

Peritoneal Cells

Macrophage

PANEL D

Test agent

Assay_Counter

Additional Agent

Thalidomide

1

Phorbol 12-myristat 13-acetate

Thalidomide

2

GM-CSF

Thalidomide

2

LPS

Thalidomide

3

GM-CSF

Thalidomide

3

IL-6

Thalidomide

4

IL-6

Thalidomide

4

LPS

Thalidomide

5

IL-6

Thalidomide

5

IL-3

Thalidomide

6

LPS

Thalidomide

33

Phorbol 12-myristat 13-acetate

*: See text for details. The amount of information displayed per query has been limited for clarity.