In this post, we’ll explore the core methods used in comparative genomics, the questions they help answer, and how they’re shaping our understanding of life.

1. Whole-Genome Alignment
Whole-genome alignment involves mapping the entire genome of one species to another. Tools like MUMmer, MAUVE, and LASTZ perform large-scale sequence alignments to detect conserved regions, rearrangements, insertions, and deletions.

Use Case:
Comparing human and chimpanzee genomes to identify evolutionary conserved sequences (ECS) and regions of divergence.

Key Challenges:
Handling repetitive sequences and genome rearrangements.

Computational complexity in large genomes.

2. Synteny and Collinearity Analysis
Synteny refers to conserved blocks of gene order across species. Tools like MCScanX, SynMap, or CHITRA (for visualizing synteny interactively) detect these blocks to understand chromosomal evolution.

Use Case:
Studying ancient genome duplications in plants.

Investigating chromosomal rearrangements in cancer genomes.

3. Ortholog and Paralog Detection
Orthologs are genes in different species that evolved from a common ancestor, while paralogs are genes duplicated within a genome. Identifying them is crucial for functional annotation and evolutionary studies.

Popular Tools:
OrthoFinder, Orthologous MAtrix (OMA), InParanoid, and EggNOG.

Use Case:
Functional prediction of uncharacterized genes based on orthologs in model organisms.

Tracing gene family evolution.

4. Phylogenomic Analysis
Phylogenomic methods combine phylogenetics and genomics to infer evolutionary trees based on genome-wide data. These methods can handle dozens to hundreds of genomes, using concatenated alignments or gene trees.

Tools:
RAxML, IQ-TREE, ASTRAL, Phylip, BEAST.

Use Case:
Resolving the evolutionary relationships between microbial species.

Studying speciation events.

5. Pan-Genome Analysis
The pan-genome consists of the core genome (shared by all strains) and the accessory genome (strain-specific genes). This is especially popular in microbial genomics.

Tools:
Roary, Panaroo, BPGA, PGAP.

Use Case:
Understanding virulence factor diversity in E. coli.

Designing broad-spectrum vaccines.

6. Comparative Transcriptomics
Comparing transcriptomes across species or conditions reveals conserved and unique expression patterns. RNA-seq data can be mapped to reference genomes to identify orthologous expression profiles.

Use Case:
Comparing stress response in extremophiles and model species.

Studying conserved regulatory networks.

7. Functional Element Comparison
Beyond genes, comparative genomics also targets non-coding regions—enhancers, promoters, miRNAs. Conservation across species often implies functional importance.

Tools:
PhastCons, GERP, phyloP (based on multiple alignments).

Use Case:
Detecting conserved non-coding elements in vertebrates.

Studying regulatory divergence in human evolution.

8. Horizontal Gene Transfer (HGT) Detection
In microbes, genes often jump across species boundaries. Comparative genomics can detect HGT by identifying genes that defy the expected phylogenetic pattern.

Tools:
HGTector, DarkHorse, AlienHunter, SIGI-HMM.

Use Case:
Tracing antibiotic resistance genes.

Exploring microbial adaptability in extreme environments.

Final Thoughts
Comparative genomics is a powerful lens to observe the diversity and unity of life. With a broad toolkit—from aligners to orthology pipelines, phylogenetic engines to visualization tools—it allows scientists to ask big questions: How did genomes evolve? What makes species unique? Where do new genes come from?

Whether you're studying extremophiles, building better crops, or exploring human ancestry, comparative genomics offers the methods to connect the dots across the tree of life.

http://www.weizmann.ac.il/plants/Milo/index.php

Our research is at the crossroad between cell biology, ecological genomics, systems biology, molecular evolution and population genetics. We study the architecture and evolution of protein and signalling networks.

More at http://landrylab.ibis.ulaval.ca/

Research Area:
pancreatic cancer; ovarian cancer; prostate cancer; bowel cancer; brain cancer; endometrial cancer; breast cancer; personalised medicine; high-throughput genomics

Link @ http://www.imb.uq.edu.au/sean-grimmond

Find more at http://www.ploscompbiol.org/article/info%3Adoi%2F10.1371%2Fjournal.pcbi.1003107

The US born Sangeeta Bhatia at Massachusetts Institute of Technology (MIT) has developed a cheap, simple, paper test that can detect cancer. These diagnostic, which works much like a pregnancy test, could reveal within minutes, based on a urine sample, whether a person have cancer or not. The MIT media announce the major and amazing breakthrough in cancer diagonistics. These newly developed technology will allow non-communicable diseases to be detect at early stage, which will be cheap and easily accessible to the masses. For the developing world it would be exciting to adapt it instead to a paper test that could be performed on unprocessed samples in a rural setting, without the need for any specialized equipment. The simple readout could even be transmitted to a remote caregiver by a picture on a mobile phone.

The MIT professor and Howard Hughes Medical Institute investigator Sangeeta Bhatia, who is also the John and Dorothy Wilson Professor of Health Sciences and Technology and Electrical Engineering and Computer Science, invented a new class of synthetic biomarker, which is highly specialized instrument to do these kind of analysis. These paper test essentially relies on nanoparticles that interact with tumor proteins called proteases, each of which can trigger release of hundreds of biomarkers that are then easily detectable in a patient's urine. The MIT nanoparticles are coated with peptides (short protein fragments) targeted by different MMPs. These particles congregate at tumor sites, where MMPs cleave hundreds of peptides, which accumulate in the kidneys and are excreted in the urine.

To create the test strips, the researchers first coated nitrocellulose paper with antibodies that can capture the peptides. Once the peptides are captured, they flow along the strip and are exposed to several invisible test lines made of other antibodies specific to different tags attached to the peptides. If one of these lines becomes visible, it means the target peptide is present in the sample. The technology can also easily be modified to detect multiple types of peptides released by different types or stages of disease.

In tests in mice, the researchers were able to accurately identify colon tumors, as well as blood clots. Bhatia says these tests represent the first step toward a diagnostic device that could someday be useful in human patients. "This is a new idea — to create an excreted biomarker instead of relying on what the body gives you," she says. "To prove this approach is really going to be a useful diagnostic, the next step is to test it in patient populations."

Reference:

Image: jasongrowclients

Homepage: http://lmrt.mit.edu/about.html

http://web.mit.edu/newsoffice/2014/a-paper-diagnostic-for-cancer-0224.html

http://timesofindia.indiatimes.com/home/science/PIO-develops-cheap-paper-test-to-detect-cancer/articleshow/30963615.cms

More at http://www.tiehh.ttu.edu/dr.-kamaleshwar-singh.html