Essential Human Genes

Presented by
Agray Chettiar - 2019B1A80980G

Vedant Gujjar - 2019B1A80957G

Roshan Singh Matharu - 2019B1A31086G

Rohit Rajesh - 2019B1A80967G

Table of Contents 1. Introduction
2. Systematic approaches to identifying
the critical components of a eukaryotic
cell
3. DEG Database
4. CRISPR-Cas9
5.CRISPR-Cas9 Genome Editing
6.Similarities in essential gene of
Eukaryotes
7. Use in Cancer Cure
8. Prediction HEG based on Deep
Learning
9. Conclusion
1. INTRODUCTION ● A gene can be defined as essential
gene when loss of its function
compromises viability of the individual
(for example, embryonic lethality) or
results in profound loss of fitness.

● Several computational methods are

available to score gene essentiality,
and recent progress has been made in
defining essentiality in the non-coding
genome.
● These studies provide the first accurate picture
of the sets of genes that are absolutely required
for the viability of individual human cell types
● Not easy to remove a gene from human body
and check its essentiality directly
● Even experimentally determined list of HEG are
proved to be elusive
● Reconciling these discrepancies in how we
evaluate gene essentiality has applications in
clinical genetics and may offer insights for drug
development.
 ● Pioneered in yeast
2. Systematic
● After few years of publication of yeast
Approaches to identify genome , yeast gene were deleted one by
one and approx. 20 % were found to be
critical components of absolutely required for the yeast cell for
survival these gene known as essential
a eukaryotic cell gene, and were shown to be used in core
mechanism of the cell like in the
ribosome, RNA polymerase, and central
metabolic enzymes

● In simple nematodes like C. elegans there

was a similar rapid movement from
genome sequence to systematic genetic
screens (A genetic screen or mutagenesis
screen is an experimental technique used
to identify and select for individuals who
possess a phenotype of interest in a
mutagenized population. Hence a genetic
screen is a type of phenotypic screen)
● This was driven by RNA-mediated
interference (RNAi) and several other
eukaryotes have followed the same path
rather than genetic engineering

● The RNAi screens revealed that more than

50% essential gene of worm were
orthologous to the yeasts essential gene
,showing that most of the essential
components being shared between the
eukaryotes
3. DEG Database

● Essential genes are those

indispensable for the survival of an
organism, and therefore are
considered a foundation of life. DEG
hosts records of currently available
essential genomic elements, such as
protein-coding genes and non-coding
RNAs, among bacteria, archaea and
eukaryotes.
● Essential genes in a bacterium
constitute a minimal genome,
forming a set of functional modules,
which play key roles in the emerging
field, synthetic biology.
4. CRISPR-Cas9 ● CRISPR is a family of DNA sequence
found in genome of prokaryotes like
bacteria, archaea etc.
● This technique is used by the bacteria to
protect themselves from infection by
virus.
● When bacteria detects the viral DNA it
produces two short RNA, one of which
containing sequence matching to that of
invading Virus.
● These two RNA’s form a complex with a
protein called Cas9.
 4. CRISPR-Cas9

● Cas9 is a nuclease, a type of

enzyme that can cut DNA
● When the matching sequence RNA
known as guide RNA, finds the viral
invading DNA genome, the Cas9
cuts the target DNA disabling the
virus
5. CRISPR-Cas9 Genome Editing

● Systematic genetic screens in human cells have

proved harder , even with the high-throughput RNAi
screens in the Human, This is how CRISPR-Cas9
genome editing came to help
● previously used techniques were too noisy, too
inefficient and too unwieldy,but the CRISPR-Cas9
genome editing is exception, it is very efficient, and
robust technique
● Recent studies use CRISPR-Cas9 based screens to
disrupt one gene at a time and assess the effect on
cell viability,while others also use a complementary
gene disruption approach, gene trapping, to randomly
disrupt all genes in a haploid human cell line
● But RNAi based screens are
less compatible with either of
the approach, especially they
are poor at detecting the low
expression gene.
● This shows the skews and the
biases of the RNAi technique
but also shows the robustness
of the CRISPR-Cas9.
6. Similarities in ● The recent studies show the general
properties of the Human essential
essential gene of gene ,and these are very similar to
that of yeasts or nematodes
Eukaryotes essential gene.
● They are highly enriched for genes
involved core cellular processes like
translation, transcription, and
metabolism; they tend to be highly
expressed; and they tend to be under
strong selective pressure.
● Which can be seen both in lower
variation rates within a species and
greater cross-species conservation.
● While most essentials are already well
characterized and highly conserved, many
uncharacterized genes also have profound
effects on viability. These data will drive
future deep studies to probe the functions
of the new essential genes
● Interestingly, the essentiality of the
eukaryotic gene is context-dependent,like
it might show strong requirement in one
condition but not in another condition and
many essential gene that are critical in one
background may have little impact on
viability in other background
 ● It is being tested that some of the
7. Use in Cancer essential genes are functional only in
specific cell lines ,this means they are
cure essential only in that specific line and not
other.
● In case of cancer cell, finding essential
gene set that are specific to that cancer
cell is important and difficult, as it is not
easy to kill the tumor cell and leave
healthy cells untouched.
● Gene that is essential for the survival of
the tumour cell are the main target of the
Chemotherapy technique to cure cancer.
● While there are also other technique that
exploit the vulnerabilities, other tumour
cell, for example, a tumour cell that has
lost BRCA1 is acutely sensitive to
inhibition of poly ADP ribose polymerase
(PARP).
Use in Cancer Cure

● This type of approaches shows not only essential

genes that are specific to the tumour cell lines exist
but also show that we can search and target them
specifically, not now but in future with new highly
selective therapies that only targets the tumour cell
leaving the healthy cells unaffected.
● But it's easier said than done, while most of the
essential gene might be useful in the cells of the
tumour, but in some cells of the same tumour it
might not be essential, and the key is to kill or
constraint all the tumour cells.
Use in Cancer Cure

● There are even problems in the delivery

of in vitro and relevance of cell based
assay
● Cancer being complex and
heterogeneous, in vitro cell assay are
limited and delivery too is hard.
● What is new for us is that for the first
time we can accurately capture the set
of genes that could potentially be
targeted to kill one cell while leaving
another untouched.
DeepHE: Accurately predicting human essential
genes based on deep learning

Summary-

Essential genes are a subset of genes. They are indispensable to the survival or reproduction of a living
organism and thus play a very important role in maintaining cellular life. The identification of gene
essentiality is very important for understanding the minimal requirements of an organism, identifying
disease genes, and finding new drug targets. Essential genes can be identified via several wet-lab
experimental methods, but these methods are often time-consuming, laborious, and costly. As a
complement to the experimental methods, some centrality measures and traditional machine learning
based computational methods have been proposed which mainly focused on predicting essential genes
on model organisms. Here, we show that human essential genes can be accurately predicted by exploring
sequence data and protein interaction network based on deep learning techniques. The ability to
accurately and efficiently predict essential genes by utilizing existing biological data accelerates the
annotation and analysis of essential genes and thus advance our understanding of the mechanism of
basic life, and boosts the drug development process
.
Deep Learning Model
Data used

Protein-protein interaction data was downloaded from

BioGRID - https://thebiogrid.org/

Sequence data was taken from the DEG (Database of

Essential Genes) dataset - http://www.essentialgene.org/
Results

AUC represents the probability that a random positive example is positioned to the right of a random negative
example. AUC ranges in value from 0 to 1. A model whose predictions are 100% wrong has an AUC of 0.0;
one whose predictions are 100% correct has an AUC of 1.0.
Conclusion

● Essential genes are a subset of genes, they are indispensable to the survival or reproduction
of a living organism and thus play a very important role in maintaining cellular life.
● The identification of gene essentiality is very important for understanding the minimal
requirements of an organism, identifying disease genes, and finding new drug targets.
● Here, we show that human essential genes can be accurately predicted by exploring
sequence data and protein interaction network based on deep learning techniques.
● The ability to accurately and efficiently predict essential genes by utilizing existing biological
omics data accelerates the annotation and analysis of essential genes, advance our
understanding of the mechanism of basic life, and boosts the drug development.
● Our new-found ability to map cell-specific essential genes may underlie the next generation
of cancer therapeutics and will drive the analysis of human gene function in a wide range of
cell-types and from diverse genetic backgrounds. Large-scale analysis of human gene
function in any cell type has long been an inelegant process, imperfect techniques yielding
imperfect data.