Biological Sequence Analysis 140.638.01. The materials used in this class are made possible by: Zhiping Weng, Wenyi.

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Presentation transcript:

Biological Sequence Analysis

The materials used in this class are made possible by: Zhiping Weng, Wenyi Wang Zhijin Wu Garland publishing, Alberts’s the Cell And the wealth of internet resources

Who are we? Sining Chen Carlo Colantuoni Giovanni Parmigiani

Who are you? Field of research Stats & computing background Register or audit Why are you taking this course Specific topics you are interested

tm Administrative Details

The MHS program in Bioinfo Jointly offered by Dept. Biostatistics and Molecular Microbiology and Immunology An intensive one-year program that emphasizes biology, statistical methods, and computing

Goal of the class Learn to look at biological sequences from a probabilistic point of view Understand algorithms behind routine operations, e.g. BLAST. Be able to build statistical model to solve problems involving sequences

Carlo Colantuoni Clinical Brain Disorders Branch, NIMH, NIH Dept. Biostatistics, JHSPH Biological Sequence Analysis: Basic Biological Concepts

Molecular Cell Biology: Central Dogma RNA Protein Sequence analysis important at all 3 levels Transcription Translation DNA Replication

The Human Genome DADMOM YOU 2 copies in every cell (46 chr) One copy from each parent Each parent passes on a “mixed copy” Genomic Content: 3.3 billion bases ~30K genes 23 chromosomes (22+X/Y) Millions of variants

Nucleotides are the chemical building block of Nucleic Acids: DNA and RNA

Nucleotides are the chemical building block of Nucleic Acids: DNA and RNA

From Genomic DNA to mRNA Transcripts EXONSINTRONS Alternative splicing ~30K >30K Protein-coding genes are not easy to find - gene density is low, and exons are interrupted by introns. Promoters Poly-Adenylation

AAAAA STARTSTOP protein coding 5’ UTR 3’ UTR mRNA Genomic DNA 3.3 Gb Protein Molecular Cell Biology: Components of the Central Dogma Transcription Translation

DNA: A T G C 1:1 RNA: A U G C 3:1 Protein: 20 amino acids Transcription Translation Replication Translation - Protein Synthesis: Every 3 nucleotides (codon) are translated into one amino acid

Translation - Protein Synthesis 5’ -> 3’ : N-term -> C-term RNA Protein

Nucleotide sequence determines the amino acid sequence

The Human Genome DADMOM YOU 2 copies in every cell One copy from each parent Each parent passes on a “mixed copy” Genomic Content: 3.3 billion bases ~30K genes 23 chromosomes (22+X/Y) Deletions Insertions Mutations Evolutionary Scale

Biological Sequence Analysis: Primary Concepts Homologue Paralogue Ortholog Identity & Similarity