Serna Bio’s Post

#RNA structure prediction is not possible at present due to a lack of abundant high-quality reference data. GARNET (Gtdb Acquired RNa with Environmental Temperatures) is a new database linking RNA sequences derived from GTDB genomes to experimental and predicted optimal growth temperatures of GTDB reference organisms, which is used to define the minimal requirements for a sequence- and structure-aware RNA generative model. #MachineLearning deployed to make connections between RNA sequence, structure, and function. https://lnkd.in/e_sYQeEA

A new database for RNA structural and functional analysis anchored to the Genome Taxonomy Database in this paper from Shulgina et al https://lnkd.in/e_sYQeEA . They define the minimal requirements for a sequence-and-structure-aware RNA generative model, and develop a GPT-like language model for RNA which is used to identify mutations in ribosomal RNA that confer increased thermostability to the Escherichia coli ribosome.

How does LINE-1 propagate in the genome? 1- First, a LINE-1 locus is de-repressed and transcribed. The mRNA is transported to the cytoplasm (polyadenylated introneless RNA). 2-In the cytoplasm, LINE-1 RNA is translated into the corresponding proteins (ORF1p & ORF2p). ORF1p amount is much more compared to ORF2p. 3-ORF1p is a chaperone that helps L1 RNA fold properly, while ORF2p has endonuclease and reverse transcriptase activities. 4-The two proteins bind to the L1 RNA in cis (the translated proteins bind to the RNA that codes for them). LINE-1 RNA and the proteins form RiboNucleoProtein (RNP) complexes. 5- RNP complexes enter the nucleus. 6- ORF2p nicks the DNA in an AT-rich region(endonuclease) and the L1 RNA poly A tail anneals to the nicked DNA. ORF2p (reverse transcriptase) makes L1 cDNA (full-length L1 or a truncated copy). This step is called Target-Primed Reverse Transcription (TPRT). 7- The cell repairs the DNA damage and a new L1 copy is integrated into the genome. Photo credit: https://lnkd.in/e63X7esr #LINE_1 #L1 #transposable_elements #retroelements #dna

ENCODE - A New "Book of Life" that redefined RNA as the master molecule 🧬ENCODE is the acronym for "Encyclopedia of DNA Elements" a project started in 2012 at Cold Spring Harbor Laboratory to put together a compendium of human DNA functions. 🧬The sequencing of human genome earlier deciphered that only 1% of the genome codes for proteins and the rest of the sequences are mostly non-coding introns and regulatory/control sequences dubbed the "Junk DNA". 🧬The findings of the ENCODE team surprisingly revealed that contrary to prior assumptions, "nearly 75% of the genome gets transcribed into RNA." This was rechristened as "non-coding RNA" or "ncRNA" and a whopping 37,600 non-coding genes were identified. 🧬The ncRNA is involved in gene regulation and it includes not simply turning the genes off or on but also fine-­tuning their activity. This means that although some genes hold the blueprint for proteins, ncRNA can control the activity of those genes and thus ultimately determine whether their proteins are made.  🧬 This redefines the 70-year-old Watson-Crick DNA double helix discovery and the subsequent "central dogma of life as enunciated by Francis Crick that "DNA makes RNA makes Protein" - the equation of life. 🧬The current hypothetical count of ncRNAs is at 500,000 of which 2000 have been specifically assigned regulatory functions that have been clinically implicated and these are the microRNAs (miRNAs). 🧬As the new "master regulatory molecules", ncRNA can be references to develop drugs that target ncRNAs involved in disease onset or, conversely, we can now use ncRNAs themselves as drugs. The article: https://lnkd.in/eZ4_U3yN

🔍Fantastic Plots and How to Read Them!🔍 Ever looked at a plot and had no idea what info to extract from it? We got you! In each post of this series we will present a common plot used for presenting DNA and RNA sequencing related results. We will then give some background on the plots' purpose and how to interpret it. Have fun and stay tuned! This week: 🍣 Sashimi Plots🍣  Most human genes are built to express more than one transcript isoform of a gene depending on a variety of inner- and extracellular factors like cell-state or temperature changes. If those alternatively spliced variants are of interest while conducting a bulk RNA-seq experiment, a fitting plot type to visualise the splice variants is essential. This is where Sashimi plots come into play! 🔍How do you read a Sashimi plot? 🧬Exons are represented by blocks in a Sashimi plot. Their length is dependent on the length of the exon they represent and their height shows the abundance of sequencing reads found for specific sequences in the exon. 🧬Introns are only represented passively as space between the exons (unless there are reads present due to intron retention). 🧬Splice junctions are shown as lines connecting the exon-blocks. They carry a number that stands for the count of sequencing reads, that were spanning this junction, which is an indicator of how often this specific splice variant was abundant in the cell. 🔍What can be extracted from a Sashimi plot? Sashimi plots are usually used to compare the splice isoforms of different conditions. Every row represents such a condition. Of course, for each condition multiple splice isoforms can occur. This is also visualised by the junction-spanning lines that hold information about every junction found in the reads and therefore about the different exon-combinations that might exist in a sample. In short, a Sashimi plot effectively conveys information about which splice forms are abundant in a sample and how that varies dependent on its state. We hope this post gave you some new insights! If you want to read more about bulk RNA-sequencing and its application in research on alternative splicing, our latest blogpost is perfect for you: https://lnkd.in/dD3BdAQ2 The plots below are from a publication by Alexander Neumann et al. (2020). They used bulk RNA-seq amongst other methods to investigate temperature-dependent alternative splicing and mRNA decay in primary mouse hepatocytes. Can you interpret their shown results? #OmiqaBioinformatics #Statistics #LifeScience #NextGenerationSequencing #bulkRNAseq

https://lnkd.in/eKcm6pza We have developed a new method for promoter sequence classification based on a genetic algorithm and the MAHDS sequence alignment method. We have created four classes of human promoters, combining 17,310 sequences out of the 29,598 present in the EPD database. We searched the human genome for potential promoter sequences (PPSs) using dynamic programming and position weight matrices representing each of the promoter sequence classes. A total of 3,065,317 potential promoter sequences were found. Only 1,241,206 of them were located in unannotated parts of the human genome. Every other PPS found intersected with either true promoters, transposable elements, or interspersed repeats. We found a strong intersection between PPSs and Alu elements as well as transcript start sites. The number of false positive PPSs is estimated to be 3 × 10−8 per nucleotide, which is several orders of magnitude lower than for any other promoter prediction method. The developed method can be used to search for PPSs in various eukaryotic genomes.

Exciting Genome editing technology in Telomere and Telomerase.

How to find DNA and RNA base composition The two main types of nucleic acids are deoxyribonucleic acid \(DNA\) and ribonucleic acid \(RNA\). DNA is the genetic material found in all living organisms, ranging from single-celled bacteria to multicellular mammals. It is found in the nucleus of eukaryotes and in the chloroplasts and mitochondria. In prokaryotes, the DNA is not enclosed in a membranous envelope, but rather free-floating within the cytoplasm. The entire genetic content of a cell is known as its genome and the study of genomes is genomics. In eukaryotic cells, but not in prokaryotes, DNA forms a complex with histone proteins to form chromatin, the substance of eukaryotic chromosomes. A chromosome may contain tens of thousands of genes. Many genes contain the information to make protein products; other genes code for RNA products. DNA controls all of the cellular activities by turning the genes on or off. The other type of nucleic acid, RNA, is mostly involved in protein synthesis. In eukaryotes, the DNA molecules never leave the nucleus but instead use an intermediary to communicate with the rest of the cell. This intermediary is the messenger RNA \(mRNA\). Other types of RNA like rRNA, tRNA, and microRNA are involved in protein synthesis and its regulation. Youtube video: https://lnkd.in/ddhqkWUW \#nikolays_genetics_lessons

Researchers have discovered a molecular oddity in bacteria that could lead to customizable genome redesign. The technique exploits the natural ability of mobile genetic sequences, called jumping genes, to insert themselves into genomes. The system, guided by an #RNA molecule called "bridge" RNA or "seekRNA," has been shown to edit genes in a bacterium and in test tube reactions. But it is still unclear whether it can be adapted to work in human cells. To find tools, the researchers screened a diverse class of enzymes that allow mobile DNA elements in bacteria to hop from one place to another. They found a family of transposable elements called IS110, which uses a complex and unusual RNA-based targeting system. By altering the sequences at either end of this bridge, the researchers were able to program IS110 enzymes to insert a cargo (up to 5kb) of their choice anywhere in the genome. The second group of researchers characterized the biochemistry of IS110 molecules and those of another family, IS1111, which use a similar mechanism and are also programmable. They call their RNA intermediaries 'seekRNA'. The IS110 and IS1111 systems require only a single protein, which is less than half the size of many of the Cas enzymes used in CRISPR genome editing systems. This size difference is important for medical applications: the viruses often used to deliver genome-editing components (#AAVs) into human cells have limited cargo capacity (4.7 kb). So far, members of the IS110 family do not appear to work well in mammalian cells, and the research team is now trying to engineer them to work better in mammalian cells. Regardless of their success, the IS110 mechanism stands out as a novel and elegant way for mobile DNA elements to hitchhike around the genome.

When the Human Genome Project researchers announced that they had successfully completed sequencing the human genome, it was only about 92% complete. There were still hundreds of gaps or missing DNA sequences. Why was it so difficult to complete the sequence? Let’s break it down! A quick refresher: DNA strands are made up of chemical units called nucleotide bases. These are adenine (A), cytosine (C), guanine (G) and thymine (T). Your body reads the order of these letters to determine the info in the strand, just as you would read a word to determine its meaning!    An organism’s complete set of DNA is called its genome. Nearly every single cell in the body contains a copy of exactly 3 billion DNA base pairs that make up the human genome. You read that right — 3 BILLION. In other words, the human genome contains a massive amount of DNA!    Researchers cannot read all 3 billion base pairs from end to end. First, they determine the sequence of random pieces of DNA. Then, they use those smaller sequences to put the whole genome sequence back together. It is a massive puzzle! Like all great puzzles, they take time.    Parts of our DNA are also painfully repetitive. Some sections of the human genome sequence are so long and repetitive that it can be difficult for researchers to put it in the right place.    Thankfully, researchers have been developing a new technology called long-read sequencing that helps to read longer, more difficult stretches of DNA. During the Human Genome Project, researchers could only read 500 bases at a time. Now, they can read over 100,000!    Researchers needed those new sequencing technologies in order to finish the last, extremely difficult 8% of the human genome. It took twice as long to sequence the last 8% of the human genome as it did the first 92%! Researchers have been developing this technology for decades.    Fancy sequencing technology cannot work without the genomic researchers who are putting in the hard work, skill and dedication. These amazing researchers are true perfectionists and finally completed the human genome sequence!    The complete human genome sequence could provide new insight into missing heritability and human disease.    Want to learn more about this epic puzzle and the work to finish it? Check out our infographic on finishing the human genome sequence! https://lnkd.in/eBZPJwP