markboguski.net

Home   Education   Employment   Publications   Presentations   Boards   Teaching   Awards
 

Functional Genomics   

  • Functional Genomics: It's All How You Read It (1997) |PubMed|PDF|  This invited Viewpoint published in Science provided an explicit and operational definition for this new field.
  • Functional Genomics (1998) |PDF|  This mini-review was commissioned for a special issue entitled Trends Guide to Bioinformatics (see also Bioinformatics: A New Era in this same issue).
  • Data Management and Analysis for Gene Expression Arrays (1998) |PubMed|PDF|  While on sabbatical at NHGRI, our group implemented the first relational database and analysis system, ArrayDB, for microarray data.
  • The Transcriptional Program in the Response of Human Fibroblasts to Serum (1999) |PubMed|PDF| This collaboration with Pat Brown's group at Stanford utilized our microarray design, based on the 10K/15K gene sets described in Box 1 in the above publication.
  • Gene Expression Informatics--It's All in Your Mine (1999) |PubMed|PDF|
  • Genes, Themes and Microarrays: Using Information Retrieval for Large-Scale Gene Analysis (2000) |PubMed|PDF| Our group was also first to apply methods of statistical text-mining to the interpretation of gene expression profiles.
  • Information Retreival Meets Gene Analysis (2002) |PDF|
  • Experimental Annotation of the Human Genome Using Microarray Technology (2001) |PubMed|PDF|  Despite the great success of bioinformatics and computational biology during the past 15 years, I had long believed that the most powerful approach to biomedical research problems is not through computational methods alone, nor is it through experimental methods alone, but rather via a synergistic fusion of the two approaches.  This paper substantiates this view and was published in the February 2001 Genome Issue of Nature, directly following the historic publication describing the initial sequencing and analysis of the human genome (Lander et al., 2001).  Why this juxtaposition?  Because, as Lander and colleagues point out in their section on “Gene content of the human genome,” computer programs for gene prediction have only limited accuracy and direct, experimental evidence of transcription is needed to validate, refine, correct or refute such predictions.  Our paper describes both conceptual and technological advances in the analysis of gene activity on a genome scale.  Up until this point in time, microarrays were widely but exclusively used for gene expression profiling and genotyping and both of these applications depended upon prior knowledge of expressed transcripts or sequence polymorphisms, respectively.  Our work showed that it was technically feasible to design arrays containing probes to every predicted, hypothetical exon in the human genome and then use these “exon arrays” to simultaneously assess the reality of predicted exons and examine differential splicing in mRNA transcripts under different conditions and in different tissue contexts.  Exon arrays still depend upon algorithmic exon predictions, although one can afford to greatly reduce the stringency of the predictions to include all potential true positives because our approach is unaffected by large numbers of false positives.  Nevertheless, gene prediction algorithms, even at low stringency, might miss transcription units they were not designed to detect.  Therefore, we went on to show in this paper that one could probe the genome for gene activity in a completely unbiased fashion using “tiling arrays” of overlapping oligonucleotide probes representing both strands of genomic DNA to completely eliminate the need for any a priori information on which parts of the genome might be expressed.  We demonstrated the potential of tiling arrays on an entire human chromosome.  Our approaches to experimental gene validation described in this paper have been widely applied to other genomes and have also stimulated the development of new algorithms and statistical tools for both the design of arrays and analysis of the derived data.

 

 

 

 

 

 

Home   Education   Employment   Publications   Presentations   Boards   Teaching   Awards

Thinking about data management and analysis for gene expression arrays during the 2nd annual Workshop on Methods and Applications of DNA Microarray Technology in  Tucson, AZ -- January 1988
 

 

© Dr. Mark S. Boguski, All rights reserved