Lecture 1: Sequence Alignments and Dot Plots

Vocabulary practice flashcards covering sequence alignments, dot plot interpretations, scoring schemes, dynamic programming algorithms (Needleman-Wunsch, Smith-Waterman, Myers-Miller), and gap penalty models.

Similarity

A resemblance between two characters or biological sequences that can arise through random chance, convergent evolution, or common ancestry.

Homology

The condition where two traits or sequences are derived from a common ancestor, with or without evolutionary modifications.

Homologous Site

A specific position in an alignment inferred to share common ancestry with corresponding residues in other sequences, even if the amino acid has been substituted.

Dot Matrix Method

A visual comparison method introduced by Gibbs & McIntyre (1970) where sequences are placed along matrix axes and a dot is plotted in cells where characters match, forming diagonal lines to reveal regions of similarity.

Dot Plot Diagonal

A continuous line of dots in a dot matrix comparison indicating uninterrupted sequence similarity or identity between two sequences.

Vertical Gap (Dot Plot)

A vertical break or shift in the diagonal line of a dot matrix indicating a deletion in Sequence 1 or an insertion in Sequence 2.

Horizontal Gap (Dot Plot)

A horizontal break or shift in the diagonal line of a dot matrix indicating a deletion in Sequence 2 or an insertion in Sequence 1.

Tandem Duplication

A duplication event where the copied sequence segment is located directly adjacent to the original sequence block.

Non-tandem Duplication

A duplication event where the copied sequence segment is placed at a separate, non-adjacent location on the same chromosome.

Stringency (Dot Plot)

A filtering threshold parameter that determines how strictly matching segments are displayed; lower stringency shows more individual matches but higher background noise, while higher stringency isolates longer conserved regions.

Identity Blocks Filtering (Filtering by word size)

A dot plot filtering technique where two sequences are divided into words of user-specified length, sorted alphabetically by word and location, and plotted only where exact word matches occur.

Sequence Alignment Score

A numerical value assessing alignment quality, calculated as $\text{Total score} = (\text{Matches} \times \text{Match Score}) - (\text{Mismatches or Gaps} \times \text{Penalty Value})$.

Global Alignment

An alignment strategy that attempts to align two sequences end-to-end across their entire lengths, best suited for sequences of similar length from closely related organisms.

• fails to identify and homologous regions

Local Alignment

An alignment strategy that searches for and aligns only the highest-scoring matching substrings between two sequences while disregarding dissimilar flanking regions.

Needleman-Wunsch Algorithm

A dynamic programming algorithm designed for global sequence alignment that builds a matrix to find the optimal path maximizing global residue matches.

Needleman-Wunsch Original Scoring Scheme

The baseline parameter set originally used by Needleman and Wunsch: Match = $1$, Mismatch = $0$, and Gap = $0$.

Smith-Waterman Algorithm

A dynamic programming algorithm designed for local sequence alignment that identifies optimal subsequence matches by applying negative weights to mismatches/gaps

• and capping minimum cell scores at zero.

Smith-Waterman Scoring Recurrence

The dynamic programming relation $M_{i,j} = \max\left(M_{i-1,j-1} + s_{i,j},\, \max_{k>0}(M_{i,j-k} - W_k),\, \max_{k>0}(M_{i-k,j} - W_k),\, 0\right)$, where the score $0$ prevents negative scores.

Smith-Waterman Original Scoring Scheme

The initial parameter set used by Smith and Waterman: Match = $1$, Mismatch = $-\frac{1}{3}$, and Gap = $-1 - \left(\frac{1}{3}\right)k$ for gap length $k$.

Myers-Miller Algorithm

A global sequence alignment algorithm operating in linear space, originally characterized by a scoring scheme of Match = $5$, Mismatch = $-4$, and Gap = $-16 - 4k$.

Affine Gap Penalty

A gap cost model expressed as $W_k = a + bk$, where $a$ is the gap opening penalty, $b$ is the gap extension penalty, and $k$ is the gap length.

Gap Opening Penalty

The parameter $a$ in an affine gap penalty model that penalizes the initial formation of a gap, typically set higher than the extension penalty due to the biological impact of insertion or deletion events.

Gap Extension Penalty

The parameter $b$ in an affine gap penalty model that adds a smaller incremental penalty for each additional base elongating an existing gap.

Transition / Transversion Scoring Scheme

A scoring model that differentiates nucleotide substitutions by assigning a milder penalty ($-1$) to transitions ($R/R$ or $Y/Y$) and a harsher penalty ($-5$) to transversions ($R/Y$).

NCBI - Blastn Scoring Scheme

The standard nucleotide BLAST parameters defined by Match = $2$, Mismatch = $-3$, and Gap penalty = $-5 - 2k$.

gap penalty equation

Wk = A + Bk

• where k is the gap length

• and a should be greater then b