Variant calling and/or genotyping

• DiscoSNP++ and discoSnpRAD: Reference-free small variant discovery (SNPs and indels)
• MindTheGap: Detection and assembly of large insertion variants
• TakeABreak: reference-free inversion discovery tool
• SVJedi: Structural Variant genotyper with long read data
• SVJedi-graph: Structural Variant genotyper with long read data using a variation graph

Sequence assembly

• MinYS: reference-guided genome assembly in metagenomics data
• MTG-link: local assembly tool for linked-read data
• Minia: De novo short read assembler
• de-novo pipeline: de-novo assembly pipeline (error correction / contigs / scaffolding) for genomes and meta-genomes
• Mapsembler2: Targeted assembly (not maintained)

Managing k-mers & indexation

• findere: simple strategy for speeding up queries and for reducing false positive calls from any Approximate Membership Query data structure.
  • fimpera extends findere adding the abundance information.
• kmtricks: modular tool suite for counting kmers, and constructing Bloom filters or kmer matrices, for large collections of sequencing data.
• kmindex is a tool for indexing and querying sequencing samples. It is built on top of kmtricks.
• back to sequences: Find sequences (reads, unitigs, genes) related to a set of kmers in large datasets, in a matter of seconds.
• Backpack Quotient Filter: k-mer indexing data structure with abundance
• short read connector: Detect similar reads from potentially large read set
• DSK: Count K-mer in sequences

Pangenome graph manipulation

• Pancat: Pangenome Comparison and Analysis Toolkit
• GFAGraphs: a Python library to handle pangenome graph files in GFA format.

Comparative metagenomics with k-mers

• Simka and SimkaMin: Comparative metagenomics for large-scale datasets
• Comparead & Commet: comparison of metagenomic datasets

Species and bacterial strains identification

• ORI: software using long nanopore reads to identify bacteria present in a sample at the strain level
• StrainFLAIR: STRAIN-level proFiLing using vArIation gRaph

General-purpose sequencing data manipulation

• GASSST: long read mapper
• Leon: short read compressor (now included in GATB-core)
• Bloocoo: short read corrector
• BCALM: Construct compacted de Bruijn graphs (unitigs)

 Protein Structure

• A_Purva: Contact Map Overlap solver
• MD-Jeep: Distance Geometry solver
• CSA: Comparative Structural Alignment

Workflow

• SLICEE: parallel execution of bioinformatics workflows

Comparative Genomics

• CASSIS: detection of rearrangement breakpoints
• PLAST: intensive bank-to-bank sequence comparison
• DRJBreakpointFinder: detection and precise localization of excision sites in proviral segments

It is possible to create a vector by typing data directly into R using the combine function ‘c’

x

same as

x

creates the vector x with the numbers between 1 and 5.

You can see what is in an object at any time by typing its name;

x

will produce the output ‘[1] 1 2 3 4 5′

Note that names need to be quoted

daysofweek ← c(‘Monday’, ‘Tuesday’, ‘Wednesday’, ‘Thursday’, ‘Friday’);

Usually however you want to input from a file. We have touched on the ‘read.table’ function already.

mydata

Now mydata is a data frame with multiple vectors

each vector can be identified by the default syntax

#if any of these are typed it will print to screen

mydata$V1 mydata$V2 mydata$V3

By default the function assumes certain things from the file

• The file is a plain text file (there are function to read excel files: not covered here)
• columns are separated by any number of tabs or spaces
• there is the same number of data points in each column
• there is no header row (labels for the columns)
• there is no column with names for the rows** [I’ll explain].

If any of these are false, we need to tell that to the function

If it has a header column

mydata header=T also works

Note that there is a comma between different parts of the functions arguments

If there is one less column in the header row, then R assumes that the 1^st column of data after the header are the row names

Now the vectors (columns) are identified by their name

#if any of these are typed it will print to screen

mydata$A mydata$B mydata$C

# Summary about the whole data frame

summary(mydata)

# Summary information of column A

summary(mydata$A)

We can shortcut having to type the data frame each time by attaching it

attach(mydata)

# summary of column B as ‘mydata’ is attached

summary(B)

Two other important options for read.table

If is is separated only by tabs and has a header

mydata

Really useful if you have spaces in the contents of some columns, so R does not mess up reading the columns . However if the columns or of an uneven length it will tell you.

If you know that the file has uneven columns

mydata

This causes R to fill empty spaces in a columns with ‘NA’ .

The last two examples will still work with our file and give the same result as with only headers=T

Graphs

to get an idea of what R is capable of type

demo(graphics)

steps through the examples, and the code is printed to the screen

We will work with simpler examples that have immediate use to biologists.

Remember to get more information about the options to a function type ‘?function’

Histogram of A

hist(mydata$A)

If there was more data we could increase the number of vertical columns with the option, breaks=50 (or another relevant number).

boxplot(mydata)

We can get rid of the need to type the data frame each time by using the attach function

# if not already done so

attach(mydata)

boxplot(mydata$A, mydata$B, name=c(“Value A”, “Value B”) , ylab=“Count of Something”)

same as

boxplot(A, B, name=c(“Value A”, “Value B”) , ylab=“Count of Something”)

Scatter plot

# if not already done so

attach(mydata)

plot(A,B) # or plot(mydata$A, mydata$B)

SAVING an image

Windows users (Rgui) RIGHT click on image and select which you want.

These instructions work for everyone.

You need to create a new device of the type of file you need, then send the data to that device

to save as a png file (easy to load into the likes of powerpoint, also great for web applications.

png(‘filename’)

boxplot(A, B, name=c(“Value A”, “Value B”) , ylab=“Count of Something”)

or to save as a pdf

pdf(‘filename’)

boxplot(A, B, name=c(“Value A”, “Value B”) , ylab=“Count of Something”)

Note

• Nothing will appear on screen, the output is going to the file
• Also it may not be saved immediately but will once the device (or R) is turned quit.

To quit R type

q() # If you save your session, next time you start R, you will have your data preloaded.

Or if you want to remain in R

dev.off() #turns of the png (or pdf etc) device, thus forces the data to save

The new features include

(i) building gene-based and supermatrix-based phylogenies using a single command,

(ii) testing and visualizing evolutionary models,

(iii) calculating distances between trees of different size or including duplications, and

(iv) providing seamless integration with the NCBI taxonomy database.

ETE is freely available at http://etetoolkit.org

Address of the bookmark: http://etetoolkit.org

lordFAST, a novel long-read mapper that is specifically designed to align reads generated by PacBio and potentially other SMS technologies to a reference. lordFAST not only has higher sensitivity than the available alternatives, it is also among the fastest and has a very low memory footprint.

Address of the bookmark: https://github.com/vpc-ccg/lordfast

https://www.nist.gov/news-events/news/2016/09/nist-releases-new-family-standardized-genomes

Address of the bookmark: https://jimb.stanford.edu/giab/

Address of the bookmark: https://github.com/awslabs/autogluon

Understanding Large Language Models

LLMs are AI systems trained on extensive datasets of natural language. Their ability to model context, identify patterns, and generate coherent language has proven invaluable across domains, including bioinformatics. By fine-tuning these models on biological datasets, researchers can unlock insights into molecular biology, systems biology, and beyond.

Key Applications of LLMs in Bioinformatics

1. Annotating Biological Data

Annotating genomic and proteomic data is fundamental yet labor-intensive. LLMs streamline this process by extracting functional annotations from literature and databases, predicting gene and protein functions, and providing automated insights.

2. Mining Scientific Literature

The exponential growth of publications presents a challenge for researchers to stay updated. LLMs can process large volumes of text to extract key findings, summarize papers, and identify trends, thereby facilitating efficient literature reviews.

3. Predicting Gene and Protein Functions

By leveraging sequence data and annotations, LLMs can predict the functions of uncharacterized genes and proteins. This capability is particularly useful for studying non-model organisms and orphan genes.

4. Drug Discovery and Repurposing

LLMs enable pattern recognition across chemical, genomic, and clinical datasets, identifying novel drug candidates and repurposing existing drugs for new therapeutic targets. They can simulate interactions between drugs and biological molecules, accelerating the discovery pipeline.

5. Generating Hypotheses for Research

LLMs analyze complex datasets to propose testable hypotheses. For example, they can predict protein-protein interactions, identify regulatory motifs, or model evolutionary processes in genomes.

Advantages of LLMs in Bioinformatics

• Scalability: LLMs process massive datasets rapidly, reducing the time required for data analysis.

• Versatility: These models adapt to diverse bioinformatics tasks, from genomic annotation to network analysis.

• Contextual Insights: By synthesizing information across disparate datasets, LLMs provide integrative insights into biological systems.

Challenges in Applying LLMs

Despite their promise, LLMs face limitations:

• Data Quality and Bias: Inaccurate or biased datasets can affect model predictions, necessitating rigorous data curation.

• Interpretability: Understanding the decision-making process of LLMs remains a critical challenge, especially in high-stakes fields like genomics and medicine.

• Resource Intensity: Training and deploying LLMs require substantial computational power, which can limit accessibility.

• Ethical Concerns: Handling sensitive genomic data raises privacy and security issues, emphasizing the need for ethical guidelines.

Future Prospects

The continued development of LLMs tailored for bioinformatics promises exciting advancements. Specialized models trained on omics data, open-access platforms, and interdisciplinary collaborations will expand the utility of LLMs. Moreover, integrating LLMs with other AI technologies, such as graph neural networks and reinforcement learning, can unlock deeper biological insights.

Conclusion

Large language models are revolutionizing bioinformatics by addressing longstanding challenges in data annotation, literature mining, and function prediction. Their ability to analyze complex biological datasets efficiently positions them as indispensable tools for modern research. As bioinformatics embraces AI, the synergy between LLMs and biological sciences holds the potential to unravel the complexities of life with unprecedented precision and scale.

Campaign calendar:

- Opening date for applications: January 30, 2020
- Deadline for applications: March 5, 2020
- Pre-selections: April-May 2020
- Final selections: May-June 2020
- Starting date for appointments: from September 2020

More at https://jobs.inrae.fr/en/open-competitions/open-competions-research-scientists-crcn

Address of the bookmark: https://rna.sysu.edu.cn/chipbase/

More at https://github.com/snakemake/snakemake-wrappers

Address of the bookmark: https://snakemake-wrappers.readthedocs.io/en/stable/