BOL: Related items

NCBI Datasets pages

BioStar — Wed, 12 Jul 2023 06:29:31 -0500

Update! Assembly and Genome record pages now redirect to new NCBI Datasets pages. NCBI Datasets is a new resource that makes it easier to find and download genome data. Learn more: https://ncbiinsights.ncbi.nlm.nih.gov/2023/07/11/ncbi-datasets-genome-assembly-pages/ #NCBICGR

Effective July 10, 2023, NCBI’s Assembly and Genome record pages now redirect to new NCBI Datasets pages. As previously announced, these updates are part of our ongoing effort to modernize and improve your user experience. NCBI Datasets is a new resource that makes it easier to find and download genome data.  

The following pages have been updated:

The NCBI Assembly record pages now redirect to the new NCBI Datasets Genome record pages that describe assembled genomes and provide links to related NCBI tools such as Genome Data Viewer and BLAST. 
The NCBI Genome record pages now redirect to the NCBI Datasets Taxonomy record pages that provide a taxonomy-focused portal to genes, genomes, and additional NCBI resources.

During this transition, you will have the option to return to the legacy Genome and Assembly record pages. We will remove the legacy pages in early 2024. 

piRNA and Bioinformatics: Decoding the Guardians of the Genome

LEGE — Sat, 07 Dec 2024 02:15:11 -0600

In the symphony of small RNAs, PIWI-interacting RNAs (piRNAs) stand out as the protectors of genomic integrity. These small, non-coding RNAs play critical roles in silencing transposable elements, regulating gene expression, and maintaining germline stability. The rise of bioinformatics has revolutionized our understanding of piRNAs, enabling researchers to decipher their biogenesis, functions, and evolutionary significance.

What Are piRNAs?

piRNAs are the largest class of small non-coding RNAs, typically 24–32 nucleotides in length. Unlike microRNAs (miRNAs) and small interfering RNAs (siRNAs), piRNAs do not rely on Dicer enzymes for maturation. Instead, they are processed from long single-stranded precursors and associate with PIWI proteins, a subclass of the Argonaute protein family.

The primary functions of piRNAs include:

Silencing Transposable Elements: By targeting transposons, piRNAs prevent genomic instability, particularly in germline cells.
Regulating Gene Expression: piRNAs modulate gene expression at transcriptional and post-transcriptional levels.
Epigenetic Modulation: They guide epigenetic modifications, such as DNA methylation, to specific genomic loci.

Challenges in piRNA Research

Studying piRNAs is fraught with challenges, including:

Short Length: Their small size complicates sequencing and alignment.
Lack of Sequence Conservation: Unlike miRNAs, piRNAs exhibit limited sequence conservation across species.
Complex Biogenesis: The intricate pathways of piRNA generation require sophisticated computational tools to unravel.

Bioinformatics: Illuminating the World of piRNAs

Bioinformatics has emerged as an indispensable tool for studying piRNAs, facilitating their discovery, annotation, and functional analysis. Here's how bioinformatics is transforming piRNA research:

1. Identification and Annotation

The discovery of piRNAs relies on next-generation sequencing (NGS) data. Bioinformatics tools such as piRNApredictor and Piano identify piRNA clusters and predict potential targets. Databases like piRBase and piRNAdb curate information about known piRNAs, their sequences, and associated proteins.

2. Mapping and Alignment

piRNAs often originate from repetitive regions, making their alignment challenging. Tools like Bowtie and STAR handle the unique mapping requirements of piRNAs, enabling accurate identification of piRNA clusters in genomes.

3. Functional Analysis

Bioinformatics approaches predict piRNA functions by analyzing their interactions with transposons, genes, and epigenetic marks. Algorithms such as TargetFinder and RIblast explore piRNA-mRNA interactions, shedding light on regulatory networks.

4. Evolutionary Studies

piRNAs are evolutionarily diverse, reflecting their roles in species-specific genomic defense. Comparative genomics tools help trace the evolution of piRNA clusters and their associated PIWI proteins across species.

5. Epigenomic Insights

piRNAs are key players in epigenetic regulation. Bioinformatics pipelines integrate piRNA data with chromatin immunoprecipitation sequencing (ChIP-seq) and DNA methylation data to uncover their role in shaping the epigenome.

Case Study: piRNAs in Germline Integrity

One of the hallmark functions of piRNAs is the suppression of transposable elements in the germline. For example, in Drosophila melanogaster, piRNAs target retrotransposons like gypsy and copia. Bioinformatics analyses revealed that these piRNAs guide PIWI proteins to transposon-derived RNA, ensuring genome stability during gametogenesis.

Clinical Relevance of piRNAs

Recent studies suggest that piRNAs may serve as biomarkers for diseases such as cancer, infertility, and neurodegenerative disorders. For instance:

Cancer: Dysregulated piRNA expression has been linked to tumorigenesis, making them potential targets for cancer therapies.
Infertility: Aberrant piRNA pathways are implicated in male infertility due to their role in spermatogenesis.
Neurodegeneration: piRNAs may regulate neuronal gene expression, highlighting their potential in neurological research.

Future Directions

The integration of bioinformatics with emerging technologies offers exciting opportunities for piRNA research:

Single-Cell Sequencing: Unveiling cell-specific piRNA expression and function.
Machine Learning: Predicting piRNA functions and targets with greater accuracy.
CRISPR-Based Tools: Editing piRNA clusters to explore their roles in vivo.

Conclusion

piRNAs are the unsung guardians of the genome, safeguarding genetic material from transposable elements and contributing to gene regulation and epigenetic programming. Bioinformatics has opened the floodgates of discovery, unraveling the complexities of piRNAs and their myriad roles in biology and disease.

As we continue to decode the piRNA landscape, these small RNAs promise to unveil big secrets about genome stability, evolution, and human health, cementing their place as a fascinating frontier in molecular biology.

NVIDIA and Arc Institute Unveil Evo 2: A Breakthrough AI for DNA Design

BioStar — Fri, 21 Feb 2025 10:39:47 -0600

NVIDIA and the Arc Institute have introduced Evo 2, a groundbreaking AI model designed to understand, predict, and generate DNA sequences. This marks a major advancement in computational biology, offering scientists an unprecedented tool to decode the genetic blueprint of life and even design entirely new biological systems.

The Power of Evo 2: AI Meets DNA

Evo 2 is the largest AI model for biology ever created, trained on an astonishing 9.3 trillion DNA "letters" (nucleotides) carefully selected from genomes spanning the entire tree of life. This massive dataset ensures that Evo 2 can recognize patterns and relationships in genetic sequences at an unparalleled scale.

For the first time, scientists can design DNA with AI, moving beyond simple sequence analysis to active DNA generation. Evo 2 enables researchers to predict, modify, and even create entire genetic sequences, opening new possibilities in medicine, agriculture, and synthetic biology.

Decoding the Dark Genome

One of the biggest challenges in genetics is understanding the non-coding regions of DNA—vast stretches of the genome that do not code for proteins but play crucial roles in regulating gene expression. These regions control when and how genes are activated, influencing everything from development to disease.

Evo 2 is designed to decode these non-coding elements, helping researchers uncover their functions and use this knowledge to develop gene-based therapies, synthetic life forms, and precision agriculture solutions.

From Reading DNA to Writing It

To put Evo 2’s impact into perspective:

Previous AI models could "read" DNA like a book, analyzing genetic sequences and identifying patterns.
Evo 2 can "write" entirely new DNA, designing functional genes, chromosomes, and even full genomes from scratch.

This means scientists can now engineer biological systems with AI, designing new proteins, metabolic pathways, and genetic circuits to address real-world challenges.

A Step Toward Generative Biology

The Arc Institute describes Evo 2 as a major step toward "generative biology"—a revolutionary approach where AI is used to create novel biological structures rather than just analyzing existing ones. This could lead to breakthroughs such as:

New medicines: AI-generated enzymes and proteins tailored for targeted therapies.
Disease-resistant crops: Genetically optimized plants for higher yield and climate resilience.
Synthetic organisms: Custom-designed microbes for bioremediation, biofuel production, and industrial applications.

An Open-Source Revolution

Unlike many proprietary AI models, Evo 2 is open source, making its capabilities accessible to researchers worldwide. This democratization of AI-driven biology means that scientists from different disciplines can collaborate, experiment, and innovate, accelerating discoveries in genetic engineering and synthetic biology.

With Evo 2, the boundaries of what’s possible in DNA design, genetic engineering, and biological innovation are being redrawn. The future of life sciences is no longer just about understanding life’s code—it’s about writing it.

FLAS: fast and high throughput algorithm for PacBio long read self-correction.

Jit — Sat, 22 Jun 2019 12:16:39 -0500

FLAS, a wrapper algorithm of MECAT, to achieve high throughput long read self-correction while keeping MECAT's fast speed. FLAS finds additional alignments from MECAT prealigned long reads to improve the correction throughput, and removes misalignments for accuracy.

Address of the bookmark: https://github.com/baoe/flas

Understanding reads mapping and flags !

Jit — Thu, 25 Apr 2019 09:06:20 -0500

Linear Alignment: An alignment of a read to a single reference sequence that may include insertions, deletions, skips and clipping, but may not include direction changes (i.e. one portion of the alignment on forward strand and another portion of alignment on reverse strand).

Chimeric Alignment: An alignment of a read that cannot be represented as a linear alignment. Typically, one of the linear alignments in a chimeric alignment is considered the “representative” alignment, and the others are called “supplementary” and are distinguished by the supplementary alignment flag.

Chimeric reads are indicative of structural variation in DNA-seq and it may indicate the presence of chimeric genes in RNA-seq.

In short, chimeric reads can be split in to two or more parts, each part would be mapped to reference(it’s not hard-clipped), the total length of the mapped part is longger than read length.

Representative alignment: A chimeric alignment that is represented as a set of linear alignments that do not have large overlaps typically has one linear alignment that is considered the representative alignment.

One read can align to multiple positions, we can find one alignmnet position which sequence do not have large overlaps, it called representative alighment, for other alignment positions, we called them supplementary alignment.

It seems that GATK can realignment those representative reads to the correctly position via RealignerTargetCreator and IndelRealigner. (WARNING: I am not quite sure if I understand this correctly. If someone could help me, please leave me a message below, thanks, thanks.)

Supplementary Alignment: A chimeric reads but not a representative reads.

Primary Alignment and Secondary Alignment: A read may map ambiguously to multiple locations, e.g. due to repeats. Only one of the multiple read alignments is considered primary, and this decision may be arbitrary. All other alignments have the secondary alignment flag.

Many-to-many pairwise alignments of two sequence sets

Poonam Mahapatra — Tue, 19 Jun 2018 08:34:15 -0500

needleall reads a set of input sequences and compares them all to one or more sequences, writing their optimal global sequence alignments to file. It uses the Needleman-Wunsch alignment algorithm to find the optimum alignment (including gaps) of two sequences along their entire length. The algorithm uses a dynamic programming method to ensure the alignment is optimum, by exploring all possible alignments and choosing the best. A scoring matrix is read that contains values for every possible residue or nucleotide match. Needleall finds the alignment with the maximum possible score where the score of an alignment is equal to the sum of the matches taken from the scoring matrix, minus penalties arising from opening and extending gaps in the aligned sequences. The substitution matrix and gap opening and extension penalties are user-specified.

Address of the bookmark: http://emboss.sourceforge.net/apps/release/6.6/emboss/apps/needleall.html

BamView: a free interactive display of read alignments in BAM data files

Neel — Fri, 09 Nov 2018 13:43:22 -0600

To run the application on UNIX from the downloaded jar file run the UNIX:

java -mx512m -jar BamView.jar

and extra command line options are given when '-h' is used:

java -jar BamView.jar -h

BAM files can be specified on the command line with the '-a' option:

java -mx512m -jar BamView.jar -a pathToFile/sorted.bam

If a BAM filename is not given on the command line BamView will prompt for a file to be entered. The BAM index file should have the same name as the BAM file but with a '.bai' suffix. Multiple BAM files can be loaded and overlaid in the viewer. To make this easier BamView will read in files that contain a list of filenames.

Address of the bookmark: http://bamview.sourceforge.net/

SVbyEye: R Package to visualize alignments between two or multiple DNA sequences

LEGE — Tue, 17 Sep 2024 02:34:57 -0500

R Package to visualize alignments between two or multiple DNA sequences including
a number of functionalities to facilitate processing of alignments in PAF format.

SVbyEye, an open-source R package to visualize and annotate sequence-to-sequence alignments along with various functionalities to process alignments in PAF format. The tool facilitates the characterization of complex SVs in the context of sequence homology helping resolve the mechanisms underlying their formation. Availability and implementation SVbyEye is available at https://github.com/daewoooo/SVbyEye.

Author: David Porubsky

Address of the bookmark: https://github.com/daewoooo/SVbyEye

Public Databases for Bioinformatics !

Jit — Tue, 23 Mar 2021 05:32:15 -0500

https://www.nature.com/articles/s41467-020-17155-y

Server Infrastructure:

File Server:

dhara: Synology 3614 Storage Appliance
4 Core Xeon
108TB disk storage
10Gb ethernet to SCG3
Access atx: dhara:5000
Has btsync server (try it - its much better than dropbox)

Compute Servers:

nandi: Kundaje and Phi Server
24 intel cores
256GB RAM
500GB of SSD storage 
36TB RAID6 local storage
4 Intel Phi's (space for 4 more GPU's)


durga: Montgomery and sensitive data
24 intel cores
256GB RAM
500GB of SSD RAID0 storage 
60TB RAID6 local storage

mitra: Bassik and Web/DB Server
24 core
256GB RAM 
500GB of SSD RAID0 storage 
36TB RAID6 local storage

vayu: Kundaje GPU server
4 core
64GB RAM 
200GB of SSD storage 
8TB RAID10 local storage
4 Nvidia GTX 970 4GB GPUs

amold: Bickel and SGE server
32 AMD core
128GB RAM 
200GB of SSD storage 
12TB RAID5 local storage

wotan: Bickel and SGE server
64 AMD core
256GB RAM 
200GB of SSD storage 
12TB RAID5 local storage

Filesystem:

/users/$USER
default home directory
full backups nightly 
nfs mount to dhara
should store code, papers, and other highly processed data here

/mnt/data/
globally accessible data
should store common data here
e.g. genomes and indexes, annotations, ENCODE data  
if you dont want this to count towards your quote you must chown

/mnt/lab_data/$LAB/
lab accessible data
should store lab project data here 
e.g. ATAC-seq prediction data, enhancer prediction, motif calls

/srv/scratch/$USER
fast local storage
not backed up, but on raid and data will never be deleted
most analysis should be performed here

/srv/persistent/$USER
fast local storage
synced nightly, but not backed up
       ie if the hard drives fail or you delete something and notice 
       within 24 hours we can recover. Otherwise not. (vs home which is 
       properly backed up )  
intermediate analysis products that would be hard to recover should be stored here 
       e.g. stochastic analysis results that need to be kept so that paper 
       results can be reproduced

/srv/www/$LABNAME/
web accessible from mitra.stanford.edu
*NOT BACKED UP*

Some parallel programming patterns:

# gzip a bunch of files
parallel gzip -- *.FILESTOGZIP

# fork example in python:
(for more detailed examples look at 
 https://github.com/nboley/grit/ grit/lib/multiprocessing_utils.py)

import os
import time
import random

import multiprocessing

class ProcessSafeOPStream( object ):
    def __init__( self, writeable_obj ):
        self.writeable_obj = writeable_obj
        self.lock = multiprocessing.Lock()
        self.name = self.writeable_obj.name
        return
    
    def write( self, data ):
        self.lock.acquire()
        self.writeable_obj.write( data )
        self.writeable_obj.flush()
        self.lock.release()
        return
    
    def close( self ):
        self.writeable_obj.close()

def worker(queue, ofp):
    # Try without this
    random.seed()
    while True:
        i = queue.get()
        if i == 'FINISHED': return
        # simulate an expensive function
        x = random.random()
        time.sleep(x/10)
        print i, x
        ofp.write("%i\t%s\n" % (i, x))

NSIMS = 10000
NPROC = 25

# populate queue
todo = multiprocessing.Queue()
for i in xrange(NSIMS): todo.put(i)
for i in xrange(NPROC): todo.put('FINISHED')

ofp = ProcessSafeOPStream( open("output.txt", "w") )

pids = []
for i in xrange(NPROC):
    pid = os.fork()
    if pid == 0:
       worker(todo, ofp)
       os._exit(0)
    else:
       pids.append(pid)  

for pid in pids:
    os.waitpid(pid, 0)

ofp.close()

print "FINISHED"

For use case 1 we obtained the following ENCODE and ROADMAP datasets https://www.encodeproject.org/files/ENCFF446WOD/@@download/ENCFF446WOD.bed.gz, https://www.encodeproject.org/files/ENCFF546PJU/@@download/ENCFF546PJU.bam, https://www.encodeproject.org/files/ENCFF059BEU/@@download/ENCFF059BEU.bam. Blacklisted regions were obtained from http://mitra.stanford.edu/kundaje/akundaje/release/blacklists/hg38-human/hg38.blacklist.bed.gz. The human genome version hg38 was obtained from http://hgdownload.cse.ucsc.edu/goldenPath/hg38/bigZips/hg38.fa.gz.

For use case 2 we used the set of narrowPeak files summarized in https://github.com/wkopp/janggu_usecases/tree/master/extra/urls.txt (archived version v1.0.1). The human genome version hg19 was obtained from http://hgdownload.cse.ucsc.edu/goldenPath/hg19/bigZips/hg19.fa.gz

For use case 3 we used the ENCODE datasets https://www.encodeproject.org/files/ENCFF591XCX/@@download/ENCFF591XCX.bam, https://www.encodeproject.org/files/ENCFF736LHE/@@download/ENCFF736LHE.bigWig, https://www.encodeproject.org/files/ENCFF177HHM/@@download/ENCFF177HHM.bam as we as the GENCODE annotation v29 from ftp://ftp.ebi.ac.uk/pub/databases/gencode/Gencode_human/release_29/gencode.v29.annotation.gtf.gz.