According to a preliminary report posted on December 19 by the COG-UK Consortium scientists, as of December 15, 1,623 variant genomes have been sequenced. In a December 21 tweet, COG-UK Consortium said that it added 2,963 more genome sequences of SARS-CoV-2, of which 942 (32%) belong to the new variant. The Consortium intends to sequence 20,000 more SARS-CoV-2 genomes in the next two weeks to further ascertain the spread of the variant.

There is no clear proof, at least not yet, that it does cause severe pandemic. But there is a justification for seriously taking the possibility. Another coronavirus lineage in South Africa has acquired one specific mutation that is also present in B.1.1.7. This variant is increasingly spreading across South Africa's coastal regions. And doctors have observed in preliminary research that individuals infected with this variant bear a higher viral load-a higher concentration of the virus in their upper respiratory tract. In many viral diseases, this is associated with more severe symptoms.

August1-2, 2014

Organised By

Centre of Excellence in Bioinformatics
Bioinformatics Infrastructure Facility
Department of Biochemistry
University of Lucknow
Lucknow-226007

Course Contents

Molecular Modeling
Homology Modeling
Molecular Docking
Post-structural Analyses

Molecular Dynamics (MD)
Simulation
Linux Introduction
Gromacs Installation

MD Simulation of Protein ligand complex
Analyses of MD
Trajectories
Visualization of Dynamic
complexes

Important Dates

Registration Begins June 25, 2014
Registration Closes July 25, 2014

Brochure : www.lkouniv.ac.in/conference/Brochure_August,%202014.pdf

• A simple intro to statistical distributions
• hypothesis testing
• linear models.

reading: http://compgenomr.github.io/book/stats.html

slides: https://github.com/BIMSBbioinfo/compgen2021/tree/main/week1/compgen2021_stats.pdf

exercises+code: https://github.com/BIMSBbioinfo/compgen2021/tree/main/week1/

Module 2: Unsupervised learning for genomics (9-15 August 2021)

• Understanding basic intuition behind machine learning approaches.
• Using unsupervised learning to cluster and visualise data points
• Dimension reduction techniques for visualisation and as input to clustering methods

reading: http://compgenomr.github.io/book/unsupervisedLearning.html

slides: https://github.com/BIMSBbioinfo/compgen2021/tree/main/week2/compgen2021_unsupervisedLearning.pdf

exercises+code: https://github.com/BIMSBbioinfo/compgen2021/tree/main/week2/

Module 3: Supervised learning for genomics (16-22 August 2021)

• Understanding and using supervised learning methods for predictive purposes
• How to measure prediction performance
• Understand and use cross-validation and related concepts

reading: http://compgenomr.github.io/book/supervisedLearning.html

slides: https://github.com/BIMSBbioinfo/compgen2021/tree/main/week3/compgen2021_supervisedLearning.pdf

exercises+code: https://github.com/BIMSBbioinfo/compgen2021/tree/main/week3/

https://github.com/BIMSBbioinfo/compgen2021

Address of the bookmark: https://github.com/BIMSBbioinfo/compgen2021

More at https://www.igib.res.in/bdmg/ScientistRecruitmentAdvt2023.pdf

Most people who have a balanced translocation have the right amount of chromosome material but it has been rearranged in some way. This may happen if two chromosomes swap pieces (a reciprocal translocation). In other cases two whole chromosomes may become stuck together (a Robertsonian translocation). This page describes what happens when someone has a reciprocal translocation.

Reciprocal chromosomal translocations occur following double-strand breaks (DSBs) in DNA when a section of one chromosome is exchanged with that of another, non-homologous chromosome. These exchanges may produce a dysfunctional fusion gene that disrupts cell growth and survival pathways, such as the translocations seen in leukemia and childhood sarcomas.

Chromosomal translocations have been well studied in cancer cell lines which are associated with two types of cancer, acute myeloid leukemia and Ewing's sarcoma, but determining how they contribute to cancer development is complicated by additional mutations and altered gene expression profiles in these cultured cells. Now, Juan Carlos Ramirez, head of the Viral Vector Facility at the Fundacion Centro Nacional de Investigaciones Cardiovasculares (CNIC) and his colleagues Raul Torres at CNIC and Sandra Rodriguez-Peralez at the Spanish National Cancer Center (CNIO) in Madrid, Spain have used a new genome editing tool, CRISPR-Cas9, to induce chromosomal translocations for the first time in a human cell line and in primary cells. The study's authors conclude by stating that the use of this technology will allow for the clarification of how and why chromosomal translocation occurs, which without doubt will allow new anti-cancer therapeutic strategies to be tackled.

Using RNA-Guided Endonuclease (RGEN) technology or CRISPR/Cas9 genome engineering technology, CNIO and CNIC researchers have shown that it is possible to obtain such chromosomal translocations. The CRISPR-Cas9 system is extremely simple to introduce a cut at the desired locus, easier to design, and cheaper than many other systems. Using the CRISPR-Cas9 system, Ramirez and his colleagues reproduced the translocations observed in Ewing’s Sarcoma (ES) and Acute Myeloid Leukemia (AML) patient cell lines in HEK293 cells and also generated the ES translocation in human mesenchymal stem cells and the AML translocation in umbilical cord blood cells.

By focusing on chromosomal translocation without the confounding characteristics of established cell lines, these new cells lines should help answer the fundamental question of what causes a cell to become cancerous. Ramirez and his team now look forward to modeling other chromosome translocations in a variety of cell types.

Reference:

http://en.wikipedia.org/wiki/Chromosomal_translocation

http://www.nature.com/ncomms/2014/140603/ncomms4964/abs/ncomms4964.html

Why Normalize RNA-Seq Data?

Normalization is a crucial step in RNA-Seq analysis for the following reasons:

• Sequencing depth: Different RNA-Seq experiments produce varying numbers of reads, making direct comparisons between samples misleading.

• Gene length: Longer genes inherently generate more reads, irrespective of their actual expression level.

• Bias reduction: Normalization mitigates technical biases, enabling meaningful biological interpretation.

TPM (Transcripts Per Million)

TPM measures the proportion of reads mapped to a transcript, normalized by transcript length and sequencing depth. It is calculated as:

Key Features:

1. Proportionality: TPM values sum to 1,000,000 across all transcripts in a sample, making it easier to compare between samples.

2. Intuitive interpretation: TPM values directly represent the abundance of transcripts in a sample.

3. Preferred for comparisons: TPM facilitates between-sample comparisons better than FPKM.

FPKM (Fragments Per Kilobase Million)

FPKM normalizes read counts by transcript length and sequencing depth, but without enforcing proportionality like TPM. It is defined as:

Key Features:

1. Historical significance: FPKM was one of the first normalization methods used for RNA-Seq.

2. Single-end vs. paired-end: In paired-end sequencing, FPKM becomes RPKM (Reads Per Kilobase Million).

3. Limited utility: FPKM values are not as robust as TPM for cross-sample comparisons due to lack of proportionality.

CPM (Counts Per Million)

CPM normalizes raw read counts by sequencing depth, without considering gene length. It is expressed as:

Key Features:

1. Simplicity: CPM is straightforward and computationally less intensive.

2. Application: Suitable for non-length-dependent analyses, such as comparing total expression levels or differential expression analysis.

3. Gene length agnostic: CPM does not correct for gene length, making it less ideal for measuring expression levels.

When to Use Each Method

• TPM: Best for comparing expression levels between samples, especially when transcript length and sequencing depth vary.

• FPKM: Useful for historical consistency but generally replaced by TPM.

• CPM: Ideal for differential expression analysis when gene length normalization is unnecessary.

Conclusion

Choosing the right normalization method depends on the specific objectives of your RNA-Seq analysis. TPM’s proportionality and robustness make it the preferred choice for most applications, while CPM serves well for differential expression studies. Although FPKM paved the way for RNA-Seq normalization, it has largely been supplanted by TPM in modern workflows. Understanding these methods and their nuances ensures accurate and meaningful interpretations of RNA-Seq data.

References:

1. Li, B., & Dewey, C. N. (2011). RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome. BMC Bioinformatics.

2. Trapnell, C., et al. (2010). Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation. Nature Biotechnology.

3. Law, C. W., et al. (2014). voom: precision weights unlock linear model analysis tools for RNA-seq read counts. Genome Biology.

Brief description: We are looking for suitable candidates in the area o computational biology/bioinformatics/genomics or related field for next-generation sequencing (NGS) data analysis for small-RNAs, RNA-Seq and targeted resequencing of plants and associated organisms. We are an interdisciplinary group where projects equally involve bioinformatics and systems biology (specially microarrays and next-generation sequencing (NGS) data analysis and its use), along with plant molecular biology, genetic engineering, field biology, and analytical plant chemistry for understanding response of plants to biotic stresses.

Essential qualification: MSc/BTech/MTech/PhD (or other suitable qualification) in disciplines preferable to bioinformatics, computational biology, computer application (or equivalent)/ ‘Advance Post-Graduate Diploma in Bioinformatics’. Proficiency in programming languages (such as Perl, C++) and/or statistics (proficient in R for example) is compulsory.

Desirable qualification: Experience in the field of genomics e.g. microarray analysis, NGS, genome annotation, database development and management, software development, systems and network biology (or related fields) will be preferred.

Application process: Applications should contain CV along with brief description (maximum 1 page) of research conducted (highlighting skills and experience) till now. Applications should be sent by e-mail to Shree Prakash Pandey, Department of Biological Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur Campus, WB, India within 14 days of this advertisement.

E-mail: sppiiserkol@gmail.com, sppandey@iiserkol.ac.in

Advertisement:

http://www.iiserkol.ac.in/announcements/adverts/671-advt_ra_shree_prakash_july_2014

Source:http://www.nejm.org/doi/full/10.1056/NEJMp1114866

Another video on precision medicine:

http://www.youtube.com/watch?v=Pi8W0yOXnzE

Precision Medicine basically intergrates bioinformatics, genomics , genetics, molecular biology and nanotechnology to deliver precise cure/diagnotics to a specific patient.

Examples:

• The drug imatinib (Gleevec) designed to inhibit an altered enzyme produced by a fused version of two genes found in chronic myelogenous leukemia.
• The breast cancer drug trastuzumab (Herceptin) works only for women whose tumors have a particular genetic profile called HER-2 positive.

E.g. source :

http://www.bionews-tx.com/news/2013/08/15/how-the-impact-of-cancer-genomics-on-precision-medicine-is-revolutionizing-cancer-treatment/

Address of the bookmark: http://www.cbsnews.com/video/watch/?id=50149783n

Scientists with a long-running Framingham Heart Study looked at 1,932 people (examination of about 1.5 million markers of genetic variations), comparing unrelated friends to unrelated strangers. They found that friends shared about 1% of their genes — a percentage much higher than those shared with strangers.This new findings made it clear that people have more DNA in common with those who are selected as friends than with strangers in the same population. 

The genes that lined up the most were olfactory genes, which deal with smell. The ones that lined up the least were immune system genes. The researchers weren't sure why that happened :/. Olfactory genes might be a straightforward explanation: People who like the same smells tend to be drawn to similar environments, where they meet others with the same tendencies.

Reference:

http://www.pnas.org/content/111/Supplement_3/10796.full

Image : http://i.kinja-img.com

Address of the bookmark: http://www.phyloxml.org/