# Presentation: 372011

## NCI Cancer Gene Index Project OverviewJune 2004 – January 2009

- Pat Blake CEO,
- Sophic Systems Alliance Inc.

**Sophic**

***Integrated Life Science Solutions***

**Biomax**

## Pilot Project Goal – Phase I

- Goal – Use automated and manual text mining to identify all genes related to cancer.  Annotate all gene/disease and gene/compound-treatment relationships for each cancer gene and manually verify role codes and evidence codes.
- NCI Thesaurus  extended to include Medline terms.  Used Controlled Vocabulary for Annotations of Role Codes and Evidence Codes
- NLP used to identify cancer genes and expand dictionaries.
- Pilot Phase - June 2004 – 8.8M Medline Abstracts - 7,867 suspect cancer genes – 4,685 manually verified “true” cancer genes – manually annotated 1,000

**Sophic**

***Integrated Life Science Solutions***

**Biomax**

## Index Automated & Manual Annotation Process Overview

**Sophic**

***Integrated Life Science Solutions***

**Biomax**

*Automatic** **Text-mining*

- Candidate DB

- Cancer TermDictionary

- Gene NameDictionary

- Medline Abstracts

*Manual Screening Steps*
*Manual** Annotation*
*Evidence Codes*
*Role Codes*

- Cancer / Gene / Drug

- DrugTermDictionary

**BioLT**Linguistic text analysis
- of Medline

## Cancer Gene Index Manual Annotation

**Sophic**

***Integrated Life Science Solutions***

**Biomax**

-  Evidence codes – based on GO evidence codes
-  Role codes – based on NCI Thesaurus
-  Role details – project specific extensions of role codes
-  Organism – defined vocabulary
-  Negation – yes/no
-  Celline – yes/no
-  Comments – free text

- Annotators read each sentence and annotate the following features

## 4 Year Index and TCGA Projects

- Phase II - Base Year - June 2005 – Updated Medline abstracts -12M Medline Abstracts – 10,000 suspect cancer genes – 5,800 manually verified “true” cancer genes – manually annotated 1,500 cancer genes.
*Sentences - 300,000*
- Phase III - Option Year 1 - June 2006 –– No Medline update - manually annotated 1,175 cancer genes.
*Sentences - 235,000*
- Phase IV - Option Year 2 June 2007 – Medline updated 1 April 2007 – 14M Abstracts – 6,610 manually verified “true” cancer genes – manually annotated 1,175 cancer genes.
*Sentences – 210,000*
- The ATLAS Project - June 2007 – Automated and manual annotation of abnormality/metastasis process for all Brain, Ovarian and Lung Cancer Genes.  Manually annotated 577 disease specific cancer genes
*Sentences – 16,000*

**Sophic**

***Integrated Life Science Solutions***

**Biomax**

## Cancer Gene Index Project – Phase V

- Phase V of the Cancer Gene Index Project will take 12 Months – 5/08 – 4/09
- Status of work in process (WIP):
- Total Cancer Genes	 		6,609
- HF Cancer Genes annotated		   310 - Delivered
- Total Genes annotated			4,964
- LF Genes to be annotated in this phase	1,649 – WIP
- 10-01-08 Medline Refresh -18M+ Abstracts – 94M+ Sentences
- 			_**Estimated 200-300 NEW Cancer Genes**_
- 			_**Of the 1649 LF Genes now 139 Genes are HF**_

**Sophic**

***Integrated Life Science Solutions***

**Biomax**

## Cancer Gene Index Project – Phase V

**5/08 – 12/08 - Annotate 310 High Frequency Sentence Count Genes (HFG)**
- In total about 4 million sentences with HFG Gene-Disease and Gene-Compound Relationships
- For the 310 genes in total 84,000 Gene-Disease and 106,000 Gene-Compound relationships exist
- 250,000 Gene-Disease and  250,000 Gene-Compound Relationship Sentences should be manually annotated
**NLP drill down approach - **Category based 80% - 20% Selection Strategy
- Each Gene-Disease and Gene-Compound relationship should be represented by at least 1 sentence
- NLP Analysis shows that with a cut-off of 10 sentences per Gene-Disease relationship and 7 sentences per Gene-Compound relationship 80% of all relationships are represented in about 185,000 sentences for both relationship types.
- Sentences for the remaining 20% of the relationships were selected  based on additional NLP filters to identify sentences relating to defined categories. Additional filters used were journal relevance based on top ten impact, passed project experience, and publication date. For each relationship type additional  65,000 sentences were selected for manual annotation with this approach.
- The selection metric yielded a coverage of ca. 85% of the NCI cancer disease categories, which is comparable to previous phases.
**NLP filters Gene – Disease Categories****	****NLP filters Gene – Compound Categories**
- A – Expression				A - Binding
- B – Abnormality				B - Regulation
- C – Biomarker				C – Resistance
- D – Therapy

**Sophic**

***Integrated Life Science Solutions***

**Biomax**

## HFG Gene-Disease Strategy

**Sophic**

***Integrated Life Science Solutions***

**Biomax**

- Q-1
- ABCD – 300 Sentences

- Q-2
- ABC – 2,500 Sentences
- BCD – 500  Sentences
- ACD – 2,300 Sentences

- Q-3
- AB - 44,000 Sentences
- AC - 23,000 Sentences
- AD - 42,000 Sentences
- BC - 7,400 Sentences
- BD - 5,700 Sentences
- CD - 7,700 Sentences

- Q-4
- A – 433,000 Sentences
- B – 150,000 Sentences
- C – 45,000 Sentences
- D – 100,000 Sentences

- Q-1 & Q-2 – Annotate all sentences.
- Q-3 – Select top 3-4 most recent  publications for each Gene-Disease relationship not in Q-1 & Q-2.
- Q-4 – Select top 3-4 most recent publications for category combinations A through D for each Gene-Disease relationship not covered in Q1-2 & 3.

## HFG – Gene-Compound Strategy

- Use GD methodology to annotate Gene-Compound relationships.  Use 3 key term categories to select at least 1 sentence for each relationship.  Categories are:
- Binding	B.  Regulation		C.  Resistance
- Annotation Process:
- Annotate sentences where binding, regulation and resistance all co-occur in the same sentence.  ABC
- Annotate sentences where two of the three key terms co-occur in the same sentence.  AB, AC, BC
- Annotate sentences where at least one of the key terms co-occur.

**Sophic**

***Integrated Life Science Solutions***

**Biomax**

| ABC – 7,800 Sentences | AB – 135,000 Sentences
AC – 6,800 Sentences
BC – 53,000 Sentences | A – 113,000 Sentences
B – 1,300,000 Sentences
C – 53,000 Sentences |
| --- | --- | --- |

## HF Methodology Preserves Overall Distribution of Association Types

## Data availability

- Available for bulk download in XML format
- _[http://](http://ncicb.nci.nih.gov/NCICB/projects/cgdcp)__[ncicb.nci.nih.gov/NCICB/projects/cgdcp](http://ncicb.nci.nih.gov/NCICB/projects/cgdcp)_
- Provides annotations to analyzed TCGA data in the Cancer Molecular Analysis Portal
- _[http://cma.nci.nih.gov](http://cma.nci.nih.gov/)_
- Integrated with additional data sources and available via a caBIG® through caBIO APIs and portlet
- _[http://cabioapi.nci.nih.gov/cabio42](http://cabioapi.nci.nih.gov/cabio42)_
- _[http://cagrid-portal.nci.nih.gov/web/guest/community](http://cagrid-portal.nci.nih.gov/web/guest/community)_

## The Cancer Gene Index in caBIG®  Resources

- caBIO Portlet
- Templated Search
- Results

- CMA Pathway
- Query

## Leveraging the Cancer Gene IndexRich Zhang

- Current State “inventory” of CGI
- All True Genes including Phase V Estimates – 6,800 Cancer Genes
- All Annotated Genes including 310 HFG
- Work in process (WIP) Genes – 1,649 LFG
- CGI Genes Biomarkers
- CGI Genes by Disease
- Brain			- Breast
- Ovarian			- Lymphoma
- Neuroblastoma
- CGI in Translational Medicine
- Dr. Thomas Reid – Gottingen University Medical Center Colon Cancer Use Case

**Sophic**

***Integrated Life Science Solutions***

**Biomax**

## The Cancer Knowledge Wave

***Integrated Life Science Solutions***

**Biomax**

- Catch-up & Maintenance

## Lessons Learned – Future Plans

- Lessons –
- Building and maintaining an up-to-date, highly-curated publicly available Cancer Gene Index is feasible.
- The longer the project takes, the more out-dated the information, the greater the cost and lost research opportunities are unknown.
- Use of the Cancer Gene Index as a backbone for all phases of fighting cancer is unlimited.
- Plans -
- Deliver first complete cycle of the Cancer Gene Index May 2009.
- Sophic pre-release briefings and workshops for caBIG community Feb – April 2009.
- Pursue funding for “catch-up cycle project”
- Deliver updated Cancer Gene Index within 12 months of initiation
- Move to quarterly maintenance to update Cancer Gene Index

**Sophic**

***Integrated Life Science Solutions***

**Biomax**

## Cancer Gene Index Project Team

- _NCI_
- Dr. George Komatsoulis
- Dr. Juli Klemm
- _Biomax_
- Dr. Klaus Heumann, Dr. Kaj Albermann, Dr. Andreas Fritz, Dr. Karsten Wenger, Dr. Dieter Maier, Dr. Beatrix Gerhard, Dr. Christian Wagner,Dr. Hilmar Ilgenfritz, Dr. Oliver Heinrich, Susanne Fackler, Dr. Silke Blumel
- _SAIC_
- Dr. Kathleen McCormick
- _Sophic_
- Pat Blake, Rich Zhang

**Sophic**

***Integrated Life Science Solutions***

**Biomax**