Predicting "Essential" Genes across Microbial Genomes: A Machine Learning Approach

Author(s):  
K. Palaniappan ◽  
S. Mukherjee
2019 ◽  
Author(s):  
Coryandar Gilvary ◽  
Neel S. Madhukar ◽  
Kaitlyn Gayvert ◽  
Miguel Foronda ◽  
Alexendar Perez ◽  
...  

ABSTRACTLoss-of-function (LoF) screenings have the potential to reveal novel cancer-specific vulnerabilities, prioritize drug treatments, and inform precision medicine therapeutics. These screenings were traditionally done using shRNAs, but with the recent emergence of CRISPR technology there has been a shift in methodology. However, recent analyses have found large inconsistencies between CRISPR and shRNA essentiality results. Here, we examined the DepMap project, the largest cancer LoF effort undertaken to date, and find a lack of correlation between CRISPR and shRNA LoF results; we further characterized differences between genes found to be essential by either platform. We then introduce ECLIPSE, a machine learning approach, which combines genomic, cell line, and experimental design features to predict essential genes and platform specific essential genes in specific cancer cell lines. We applied ECLIPSE to known drug targets and found that our approach strongly differentiated drugs approved for cancer versus those that have not, and can thus be leveraged to identify potential cancer repurposing opportunities. Overall, ECLIPSE allows for a more comprehensive analysis of gene essentiality and drug development; which neither platform can achieve alone.


Author(s):  
Olufemi Aromolaran ◽  
Damilare Aromolaran ◽  
Itunuoluwa Isewon ◽  
Jelili Oyelade

Abstract   Essential genes are critical for the growth and survival of any organism. The machine learning approach complements the experimental methods to minimize the resources required for essentiality assays. Previous studies revealed the need to discover relevant features that significantly classify essential genes, improve on the generalizability of prediction models across organisms, and construct a robust gold standard as the class label for the train data to enhance prediction. Findings also show that a significant limitation of the machine learning approach is predicting conditionally essential genes. The essentiality status of a gene can change due to a specific condition of the organism. This review examines various methods applied to essential gene prediction task, their strengths, limitations and the factors responsible for effective computational prediction of essential genes. We discussed categories of features and how they contribute to the classification performance of essentiality prediction models. Five categories of features, namely, gene sequence, protein sequence, network topology, homology and gene ontology-based features, were generated for Caenorhabditis elegans to perform a comparative analysis of their essentiality prediction capacity. Gene ontology-based feature category outperformed other categories of features majorly due to its high correlation with the genes’ biological functions. However, the topology feature category provided the highest discriminatory power making it more suitable for essentiality prediction. The major limiting factor of machine learning to predict essential genes conditionality is the unavailability of labeled data for interest conditions that can train a classifier. Therefore, cooperative machine learning could further exploit models that can perform well in conditional essentiality predictions. Short abstract Identification of essential genes is imperative because it provides an understanding of the core structure and function, accelerating drug targets’ discovery, among other functions. Recent studies have applied machine learning to complement the experimental identification of essential genes. However, several factors are limiting the performance of machine learning approaches. This review aims to present the standard procedure and resources available for predicting essential genes in organisms, and also highlight the factors responsible for the current limitation in using machine learning for conditional gene essentiality prediction. The choice of features and ML technique was identified as an important factor to predict essential genes effectively.


Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 1552-P
Author(s):  
KAZUYA FUJIHARA ◽  
MAYUKO H. YAMADA ◽  
YASUHIRO MATSUBAYASHI ◽  
MASAHIKO YAMAMOTO ◽  
TOSHIHIRO IIZUKA ◽  
...  

2020 ◽  
Author(s):  
Clifford A. Brown ◽  
Jonny Dowdall ◽  
Brian Whiteaker ◽  
Lauren McIntyre

2017 ◽  
Author(s):  
Sabrina Jaeger ◽  
Simone Fulle ◽  
Samo Turk

Inspired by natural language processing techniques we here introduce Mol2vec which is an unsupervised machine learning approach to learn vector representations of molecular substructures. Similarly, to the Word2vec models where vectors of closely related words are in close proximity in the vector space, Mol2vec learns vector representations of molecular substructures that are pointing in similar directions for chemically related substructures. Compounds can finally be encoded as vectors by summing up vectors of the individual substructures and, for instance, feed into supervised machine learning approaches to predict compound properties. The underlying substructure vector embeddings are obtained by training an unsupervised machine learning approach on a so-called corpus of compounds that consists of all available chemical matter. The resulting Mol2vec model is pre-trained once, yields dense vector representations and overcomes drawbacks of common compound feature representations such as sparseness and bit collisions. The prediction capabilities are demonstrated on several compound property and bioactivity data sets and compared with results obtained for Morgan fingerprints as reference compound representation. Mol2vec can be easily combined with ProtVec, which employs the same Word2vec concept on protein sequences, resulting in a proteochemometric approach that is alignment independent and can be thus also easily used for proteins with low sequence similarities.


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