🔍 Lalign: Optimal Local Pairwise Sequence Alignment

Lalign is a bioinformatics tool from the FASTA package that performs optimal local pairwise sequence alignments. It's designed to find the best-matching segments between two sequences, even if the sequences are largely unrelated overall. This makes it highly effective for identifying conserved domains, motifs, or short regions of homology.

❓ What is Lalign?

Lalign implements a variation of the Smith-Waterman algorithm to identify one or more optimal local alignments between two sequences (protein or nucleic acid). Unlike global alignment tools, Lalign focuses on finding regions of highest similarity, which may not span the entire length of the sequences.

  • Local Alignment: Identifies the most similar segments within two sequences.

  • Optimal Matches: Finds the highest-scoring local alignments.

  • Versatile Input: Supports both protein and nucleic acid sequences.

🎯 Why Use Lalign? For Pinpointing Conserved Regions

Lalign is an indispensable tool for:

  • 🔍 Domain & Motif Discovery: Precisely locating conserved functional domains or short sequence motifs shared between sequences, even in otherwise divergent sequences.

  • 🧬 Fragment Matching: Identifying where a short sequence (e.g., a primer, probe, or peptide) matches within a much longer sequence.

  • 📊 Homology Search: Discovering homologous regions in distantly related sequences or sequences with large insertions/deletions.

  • 🎯 Gene Fusion Detection: Helping to identify potential gene fusion events by finding highly similar segments from different parent genes.

  • 📈 Sequence Annotation: Annotating specific regions of a sequence based on matches to known functional elements.

🧑‍💻 How to Use Lalign on Job Dispatcher: A Step-by-Step Guide

Follow these simple steps to perform a local pairwise sequence alignment with Lalign:

1️⃣ Navigate to the Tool

  1. From the main menu, go to All Tools (or search for "Lalign").

  2. Click the prominent Use Tool button located next to "Lalign."

2️⃣ Input Your Sequences

  • Locate the two input boxes (large text areas labeled "1st Input Sequence" and "2nd Input Sequence") or the corresponding "upload a Sequence File" options.

  • Paste your sequences in FASTA format or upload FASTA files. Lalign supports both protein and nucleic acid sequences. (For an instance, in Protein)

  • Input Sequence A (1st Input Sequence):

    >seqA
MGDVEKGKKIFIMKCSQCHTVEKGGKHKTGPNLHGLFGRKTGQAPGYSYTAANKNKGIIWGEDTLMEYLENPKKYIPGTKMIFVGIKKKEERADLIAYLKKATNE
    ```

  • Input Sequence B (2nd Input Sequence):

    >seqB
MGDVEKGKKIFVQKCAQCHTVEKGGKHKTGPNLHGLFGRKTGQAAGFSYTDANKNKGITWGEDTLMEYLENPKKYIPGTKMIFAGIKKKGERADLIAYLKKATNE
    ```

  • Important: For each input, you can provide a sequence either by typing into the text area OR by uploading a file, but not both simultaneously. Please clear one input to proceed for both sequences.

3️⃣ Configure Parameters

  • 📝 Title: Provide a descriptive title for your job (e.g., "My Lalign Analysis").

  • 💡 Sequence Type: Select the type of sequence you are submitting:

    • Protein
    • DNA

  • 📊 MATRIX (matrix): Select the scoring matrix to use for your alignment.

    • BL50 (BLOSUM50) - Default
    • BL62 (BLOSUM62)
    • BP62 (BLASTP62)
    • BL80 (BLOSUM80)
    • P250 (PAM250)
    • P120 (PAM120)
    • M40, M20, M10 (MDM matrices)
    • VT160, VT120, VT80, VT40, VT20, VT10 (VTML matrices)

  • ➖ GAP OPEN (gapopen): The penalty for opening a new gap in the alignment.

    • Default: -12
    • Options: -23, -22, ..., 0 (various negative and zero values)

  • ➖ GAP EXTEND (gapext): The penalty for extending an existing gap.

    • Default: -2
    • Options: 0, -1, -2, ..., -16 (various negative values)

  • 📉 E() THRESHOLD (expthr): The expectation value (E-value) threshold for reporting matches. Lower values indicate more significant matches.

    • Default: 10.0
    • Options: 1.0e-24, 1.0e-12, 1.0e-6, 1.0e-4, 0.01, 0.1, 1.0, 10.0, 100.0

  • ⚙️ OUTPUT FORMAT (format): Choose the desired output format for your alignment results.

    • 0 (MARKX 0) - Default
    • 1 (MARKX 1)
    • 2 (MARKX 2)

  • 📈 GRAPHICS (graphics): Choose whether to output graphical representation.

    • true - Default
    • false

4️⃣ Submit Your Job

  • Once your sequences are entered and parameters are set, click the Submit or Run button.

  • Your job will be dispatched to the EMBL-EBI Web Service. You will be automatically redirected to a Job Status page to monitor its progress.

5️⃣ Interpret Results

  • On the results page, you will find one or more local pairwise alignments, highlighting the most similar regions between your two sequences.
  • The output will typically show the aligned segments, their scores, and potentially graphical representations, depending on your chosen format.
  • ⭐ Tip: Lalign is highly effective for finding short, highly conserved regions or domains within sequences that might otherwise be very different.

💬 Need Help?

If you run into issues, please visit our Contact Us page for support. Happy analyzing!