Address of the bookmark: http://fantom.gsc.riken.jp/zenbu/

What is PhyloHerb: PhyloHerb is a wrapper program to process genome skimming data collected from plant materials. The outcomes include the plastid genome (plastome) assemblies, mitochondrial genome assemblies, nuclear ribosomal DNAs (NTS+ETS+18S+ITS1+5.8S+ITS2+28S), alignments of gene and intergenic regions, and a species tree. It is designed to be a high throughput program dealing with lower quality data. Examples include low-coverage (5x cpDNA) plastome phylogeny, recycling plastid genes from target enrichment data, retrieving low-copy nuclear genes from medium coverage (5x nucDNA) genome skimming.

License: GNU General Public License

Citation:

• Cai, Liming, Hongrui Zhang, and Charles C. Davis. 2022. PhyloHerb: A high‐throughput phylogenomic pipeline for processing genome‐skimming data. Applications in Plant Sciences 10(3): 1–9. https://doi.org/10.1002/aps3.11475

Address of the bookmark: https://github.com/lmcai/PhyloHerb/

 UPARSE >
OTU clustering for 16S and other marker genes. Highly accurate OTU sequences and improved diversity measures. UCHIME >
Chimeric sequence detection. PILER >
De novo genome repeat finder. PILER-CR >
Detection of CRISPR repeats in bacterial genomes. QSCORE >
Compare two multiple alignments for benchmarking. PALS >
Whole-genome alignment. PREFAB >
Protein Reference Alignment Database. MSA benchmark collection >
Selected multiple alignment benchmarks in a standardized FASTA format.

Address of the bookmark: http://drive5.com/software.html

Address of the bookmark: https://cran.r-project.org/web/packages/vcfR/vignettes/visualization_1.html

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

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

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.

Other tools

https://github.com/shenwei356/taxonkit

• ETE, version: 3.1.1
• BioPython, version: 1.73
• taxadb, version: 0.10.1
• TaxonKit, version: 0.5.0

Address of the bookmark: https://pypi.org/project/ete3/3.1.1/

https://csgillespie.github.io/efficientR/

https://r-graphics.org/

https://rstudio-education.github.io/hopr/

https://r-pkgs.org/

https://r4ds.had.co.nz/

Address of the bookmark: https://r-graphics.org/

 https://academic.oup.com/bioinformatics/article/34/15/2666/4934939

Address of the bookmark: https://github.com/wdecoster/nanoQC

Following are the list of Ancestral /sequence/ reconstruction (ASR) tools: 

inferCars

Reconstructs contiguous regions of an ancestral genome. Given information about adjacencies between conserved segments in each modern species, our goal is to infer segment order in the ancestral genome. To get a clean and precise statement of the problem, we formalize it using graph theory. We develop an algorithm that identifies a most parsimonious scenario for the history of each individual adjacency, although the whole-genome prediction is not guaranteed to optimize traditional measures like the number of breakpoints. We introduce weights to the graph edges to model the reliability of each adjacency.

ANGES:reconstructing ANcestral GEnomeS maps

A suite of Python programs that allows reconstructing ancestral genome maps from the comparison of the organization of extant-related genomes. ANGES can reconstruct ancestral genome maps for multichromosomal linear genomes and unichromosomal circular genomes. It implements methods inspired from techniques developed to compute physical maps of extant genomes.

Cocos

Constructs phylogenies of multi-domain proteins. With a given species tree and domain phylogenies, the procedure infers the composition of ancestral multi-domain proteins. Cocos implements and extend a suggested algorithmic approach by Behzadi and Vingron in an easy-to-use program. Such method could be applied to reconstruction of partial homologous units such as bacterial operons or protein complexes.

MySSP

Constructs an initial DNA sequence at the root of the tree and simulates evolution across the tree using a variety of common models of DNA evolution. MySSP is a program for the simulation of DNA sequence evolution across a phylogenetic tree. It is designed for large-scale studies, including simulation of multiple replicates and outputs sequences into NEXUS, MEGA, or FASTA formats. MySSP has a fairly simple graphical user interface (GUI) for basic use, but also has a specialized batch script interpreter to allow for more complicated or large-scale simulations.

PARANA: Parsimonious Ancestral Reconstruction And Network Analysis

Performs parsimony based inference of ancestral biological networks. Given multiple extant networks and phylogenetic information relating extant nodes, PARANA finds a parsimonious set of ancestral interaction events (edge gains and losses) which explain the extant networks. The framework adopted by PARANA is able to represent network evolution under models that support gene duplication and loss and independent interaction gain and loss. The method works on both directed and undirected networks and can incorporate asymmetric interaction gain and loss costs. In contrast to previous approaches, PARANA does not require knowing the relative ordering of unrelated duplication events and thus, works on phylogenetic trees even where branch lengths are not provided.

GapAdj: Gapped Adjacencies

A synteny-based method that is flexible enough to handle a model of evolution involving whole genome duplication events, in addition to rearrangements, gene insertions, and losses. Ancestral relationships between markers are defined in term of Gapped Adjacencies, i.e. pairs of markers separated by up to a given number of markers. It improves on a previous restricted to direct adjacencies, which revealed a high accuracy for adjacency prediction, but with the drawback of being overly conservative, i.e. of generating a large number of contiguous ancestral regions (CARs).

ANCESTOR

A web server allowing one to easily and quickly perform the last three steps of the ancestral genome reconstruction procedure. Ancestors implements several alignment algorithms, an indel maximum likelihood solver and a context-dependent maximum likelihood substitution inference algorithm. The results presented by the server include the posterior probabilities for the last two steps of the ancestral genome reconstruction and the expected error rate of each ancestral base prediction.

ProCARs

Reconstructs ancestral gene orders as contiguous ancestral regions (CARs) with a progressive homology-based method. ProCARs runs from a phylogeny tree (without branch lengths needed) with a marked ancestor and a block file. This homology-based method is based on iteratively detecting and assembling ancestral adjacencies, while allowing some micro-rearrangements of synteny blocks at the extremities of the progressively assembled CARs. The method starts with a set of blocks as the initial set of CARs, and detects iteratively the potential ancestral adjacencies between extremities of CARs, while building up the CARs progressively by adding, at each step, new non-conflicting adjacencies that induce the less homoplasy phenomenon. The species tree is used, in some additional internal steps, to compute a score for the remaining conflicting adjacencies, and to detect other reliable adjacencies, in order to reach completely assembled ancestral genomes.

FastML

A user-friendly tool for the reconstruction of ancestral sequences. FastML implements various novel features that differentiate it from existing tools: (i) FastML uses an indel-coding method, in which each gap, possibly spanning multiples sites, is coded as binary data. FastML then reconstructs ancestral indel states assuming a continuous time Markov process. FastML provides the most likely ancestral sequences, integrating both indels and characters; (ii) FastML accounts for uncertainty in ancestral states: it provides not only the posterior probabilities for each character and indel at each sequence position, but also a sample of ancestral sequences from this posterior distribution, and a list of the k-most likely ancestral sequences; (iii) FastML implements a large array of evolutionary models, which makes it generic and applicable for nucleotide, protein and codon sequences; and (iv) a graphical representation of the results is provided, including, for example, a graphical logo of the inferred ancestral sequences.

maxAlike

Reconstructs a genomic sequence for a specific taxon based on sequence homologs in other species. The input is a multiple sequence alignment and a phylogenetic tree that also contains the target species. For this target species, the algorithm computes nucleotide probabilities at each sequence position. Consensus sequences are then reconstructed based on a certain confidence level.

MLGO: Maximum Likelihood for Gene Order Analysis

A web tool for the reconstruction of phylogeny and/or ancestral genomes from gene-order data. MLGO was designed for analysis of large-scale genomic changes including not only rearrangements but also gene insertions, deletions and duplications. MLGO can be used to infer a phylogeny from genome rearrangement and gene order data, and can also obtain an estimation of ancestral genomes, given an input tree. MLGO takes the advantage of binary encoding on gene-order data, supports a fairly general model of genomic evolution (rearrangements plus duplications, insertions, and losses of genomic regions), and successfully accommodates itself into the framework of maximized likelihood.

Image Reference : Wiki