1965 – 1970	B.Sc. in Applied Mathematics and M. Sc. in Computer Sciences, the faculty of mathematics at the Moscow State University, Moscow, USSR
1971 – 1973	Ph.D. studies (A.B.D.), Computer Sciences and Software Engineering at the Space Research Institute, USSR Academy of Sciences, Moscow, USSR
1988 – 1992	Ph.D. in Structural Biology, thesis on “Sequence Determinants of Nucleic Acids Higher Order Organization” at the Weizmann Institute of Science, Rehovot, Israel under the supervision of Professor E.N. Trifonov. The degree was granted in 1993.
1993 – 1995	Post-doctoral fellow, research associate in Biomathematics and Computational Biology at the Institute for Biological Sciences, National Research Council of Canada, Ottawa, Canada. Research subjects: a) multiple alignment methods; b) sequence determinants of the nucleosomal pattern. The supervisor: Michael Zuker.
1995 – 1996	Post-doctoral fellow in Computational Biology for Genome Research at the Departments of Membrane Research & Biophysics and the Structural Biology in the Weizmann Institute of Science, Rehovot, Israel. Research subjects: a) multiple alignment methods; b) sequence determinants of the nucleosomal pattern. The supervisors: Professors D. Lancet and E.N. Trifonov.

Scientific Professional Activities

1998- present	Institute of Evolution, Haifa University, Haifa, Israel	Associate Professor
1998 - 1998	National Institutes of Health, National Center of the Biotechnological Information at the National Library of Medicine, Bethesda, USA	Visiting Scientist
1996 – 1997	The Center for Biological Sequence Analysis at the Technical University of Denmark in Lyngby, Denmark	Research Associate Professor
1995 – 1996	Department of Computer Systems at the Center of Technological Education, Holon, Israel	Lecturer

Current Research & Interests

In general, I am interested in Computational Molecular Biology, Molecular Evolution, Structural Biology and Bioinformatics. Much of my recent research centers on biological role of evolutionary preserved genomic patterns. These patterns have been and should be revealed using methods of sequence comparison. The topics of major investigations are evolution of coding and noncoding DNA in prokaryotes, hidden messages in retroviruses, nucleosome DNA sequence pattern, splicing junction recognition.

Bioinformatics Expertise: multiple sequence alignment algorithms, sequence complexity, pattern recognition, non-linear regression, heuristic methods of optimization.

Previous Experience: data structures, programming languages, real-time programming, formal grammars, interpreters and macroprocessors.

Teaching

Courses

2002	Bioinformatics	M. Sc. in evolutionary biology
1999-2001	Computational Biology	B. Sc. in mathematics and computer science
2001-2003	Introduction to Molecular Virology	B. A.
2000-2003	AIDS: Science and Society	B. A.
1996	Data Structures	B. A. in computer science
1995	Introduction to Computing	B. A. in computer science

Instruction

Supervisor of 5 doctoral theses.

Membership in learned societies

International Society of Computational Biology

Israeli Society of Computational Biology and Bioinformatics

Conference Organization

1997	DNA Overall Macrostructure	Lyngby, Denmark
2001	Genome Organization, Diversity, and Evolution	Haifa, Israel
2003	Computational Advances to RNA World	Haifa, Israel

Grants

Title of project

Source

Total grant

From date

To date

String Matching on a Genomic Level: Theory and Practice

F.I.R.S.T.

The Israel Academy of Science and Humanities Humanities

$40,000

12/2000

12/2003

Statement of Research Interests

1. Evolution of noncoding DNA.

1.1 Simple sequence repeats. The DNA sequence is rapidly emerging from the Genome Projects. The objective of this study is to apply statistical and bioinformatics tools to identify SSRs and their variants (polymorphisms). The manuscript on this topic was published in Bioinformatics in 2002.

1.2 Regulatory sequences. We developed a tool called “linguistic complexity” (LC), and used this tool to discover potential regulatory sites through the construction of typical patterns of LC distribution in certain regions. The manuscript on this topic was published in Bioinformatics in 2002.

1.3 Curved DNA. With regards to the prokaryotic genomes, this topic was narrowed down to the “Evolution of prokaryotic promoters and terminators”. We continue study started in “Bolshoy & Nevo (2000) Ecological genomics of DNA: upstream bending in prokaryotic promoters”. There we analyzed the distribution of predicted intrinsic curvature along all complete prokaryotic genomes. We have submitted a paper related to the biological role of DNA curvature downstream to the end of translation, and a paper verifying our earlier hypothesis that the DNA curvature plays a biological role in gene regulation in mesophilic as against hyperthermophilic prokaryotes.

2. Evolution of retroviruses My PhD student Ofer Peleg and I concentrated our efforts on study of “Factors of Sequence Conservation in HIV-1 Genome”. We published a few papers on the topic.

3. Sequence pattern extraction We work on recognition and extraction of the DNA nucleosomal pattern (eukaryotes), and transcription regulatory patterns (prokaryotes).

Awards

1995	Bat-Sheva de Rothschild foundation	Post-doctoral fellowship for Genome Research, in Computational Biology	For two years
1998	Rashi foundation	Guastella Professorship	For two years

List of Publications

1. Bolshoy A. (1971) “On LR(k) Attribute and Equivalent Transformations of Grammars” (in Russian) in Numerical Methods and Computing (Problems of Computer Science), vol. XVII, pp. 9 - 12, eds. Zhogolev, Kabanov and Trofimov, Moscow State University Press, Moscow.

2. McNamara, P., Bolshoy, A., Trifonov, E.N. and Harrington, R.E. (1990) “Sequence-dependent kinks induced in curved DNA.” Journal of Biomolecular Structure and Dynamics, 8, 529 - 538

3. Bolshoy, A., McNamara, P., Harrington, R.E. and Trifonov, E.N. (1991) “Curved DNA without AA: experimental estimation of all 16 wedge angles.” Proceedings of the National Academy of Sciences of the USA, 88, 2312 - 2316

4. Ioshikhes, I., Bolshoy, A. and Trifonov, E.N. (1992) “Preferred positions of AA and TT dinucleotides in aligned nucleosomal DNA sequences.” Journal of Biomolecular Structure and Dynamics, 9, 1111 - 1117

5. Shpigelman, E., Trifonov, E.N. and Bolshoy, A. (1993) “CURVATURE: software for the analysis of curved DNA.” Computer Applications in Biosciences, 9, 435 - 440

6. Dubochet, J., Bednar, J., Furrer, P., Stasiak, A.Z., Stasiak, A. and Bolshoy, A. (1994) “Determination of the DNA helical repeat by cryo-electron microscopy.” Nature Structural Biology, 1, 361 - 363

7. Bolshoy, A. (1995) “CC dinucleotides contribute to the bending of DNA in chromatin.” Nature Structural Biology., 2, 446-448

8. Ioshikhes, I., Bolshoy, A., Derenshteyn, K., Borodovsky, M. and Trifonov, E.N. (1996) “Nucleosomal DNA Sequence Pattern Revealed by Multiple Alignment of Experimentally Mapped Sequences.” Journal of Molecular Biology, 262, 129-139

9. Bolshoy, A., Ioshikhes, I. and Trifonov, E.N. (1996) “Applicability of the multiple alignment algorithm for detection of weak patterns: periodically distributed DNA pattern as a study case.” Computer Applications in Biosciences, 12, 383-389

10. Bolshoy, A., Shapiro, K., Trifonov, E.N. and Ioshikhes, I. (1997) “Enhancement of the nucleosomal pattern in sequences of lower complexity.” Nucleic Acids Research, 25, 3248-3254

11. Ussery, D.W., Higgins, C.F. and Bolshoy, A. (1999) “Environmental influences on DNA curvature.” Journal of Biomolecular Structure and Dynamics, 16, 811-823

12. Gabrielian, A. and Bolshoy, A. (1999) “Sequence complexity and DNA curvature.” Computers & Chemistry 23, 263-274

13. Gabrielian, A. E., Landsman, D., and Bolshoy, A. (1999) “Curved DNA in promoter sequences” In Silico 1, 183-196

14. Bolshoy, A. and Nevo, E. (2000) “Ecological genomics of DNA: Upstream bending in prokaryotic promoters” Genome Research 10, 1185-1193.

15. Troyanskaya O.G., Arbell O., Koren Y., Landau G.M. and Bolshoy A. (2002) “Sequence Complexity Profiles of Prokaryotic Genomic Sequences: A Fast Algorithm for Calculating Linguistic Complexity”, Bioinformatics, 18, 679-688

16. Peleg O., Brunak S., Trifonov E.N., Nevo E. and Bolshoy A. (2002) “RNA Secondary Structure and Sequence Conservation in C1 Region of Human Immunodeficiency Virus Type 1 env Gene”, AIDS Research and Human Retroviruses, 18, 867-878

17. Kirzhner V.M, Korol A.B., Bolshoy A., and Nevo E. (2002) “Compositional spectrum – revealing patterns for genomic sequence characterization and comparison.” Physica A, 312, 447-458

18. Kirzhner V.M, Korol A.B., Nevo E. and Bolshoy A. (2003) “One promising approach to a large scale comparison of genomic sequences” Acta Biotheoretica, 51, 73-89

19. Peleg O., Trifonov E.N. and Bolshoy A. (2003) “Hidden Messages with RNA Secondary Structure Feature along the nef Gene of Human Immunodeficiency Virus Type 1” Nucleic Acids Res., 31, 4192-4200

20. Bolshoy A. (2003) “DNA Sequence Analysis Linguistic Tools. Review” Appl. Bioinform, 2, 103-112

21. Kato M., Onishi Y., Wada-Kiyama Y., Abe T., Ikemura T., Kogan S., Bolshoy A., Trifonov E.N. and Kiyama R. (2003) “Dinucleosome DNA of Human K562 Cells: Experimental and Computational Characterizations” J. Mol. Biol., 332, 111-125

22. Kalendar R., Vicient C., Peleg O., Anamthawat-Jonsson K., Bolshoy A. and Schulman A. (2003) “LARD retroelements: Major, non-autonomous, components of barley and related genomes” Genetics, in press

23. Kirzhner V.M., Korol A.B., Bolshoy A. and Nevo E. “Large-scale DNA organization: extensive sets of words distinguish genomes across life” – submitted

24. Hosid S. and Bolshoy A. “New elements of the termination of transcription in prokaryotes” – submitted

25. Peleg O., Kirzhner V., Trifonov E.N. and Bolshoy A. “Overlapping messages and survivability” – submitted

26. Hosid S., Trifonov E.N. and Bolshoy A. “Sequence periodicity in intergenic regions of Escherichia coli” – submitted

27. Kozubay-Avraham L., Hosid S. and Bolshoy A. “Curvature distribution in prokaryotic genomes” - submitted

List of manuscripts in preparation

1. Bolshoy A., Peleg O. and Trifonov E.N. “Overlapping messages in human immunodeficiency virus type 1”

2. Bolshoy A., Tatusov R., Wolf Y. and Koonin E. “Environment implies average gene length: comparative analysis of complete genomes”

3. Hosid S., Trifonov E.N. and Bolshoy A. “Dinucleotide periodicity in genomic vs. random texts”

4. Peleg O., Trifonov E.N. and Bolshoy A. “The Rabbit Ears of V3”

Curriculum Vitae and List of Publications

Total grant