ABSTRACT

Progress in medicine has always been closely tied to technical advancements, and
many recent discoveries and advancements in health and science have been no
exception. The field of pharmacology is reliant on new tools and procedures
developed by the pharmaceutical industry. Computer science is the study of
computers. Data from new modalities, including genomics and imaging, as well as
new sources such as wearables and the Internet of Things, has propelled medicine
into the digital era. We are creating targeted therapeutics to customize treatments
as we get a better knowledge of disease biology and how diseases affect
individuals. Technology such as Artificial Intelligence (AI) is required to enable
predictions for individualized treatments. We must solve challenges like as
explainability, liability, and privacy in order to mainstream AI in healthcare. Many
of the ideas that can help relieve these worries include developing explainable
algorithms and adding AI training in medical education. With the resurgence of
artificial intelligence in particular, through intelligence and the resurgence of
machine learning. Many researchers are suggesting the use of deep neural
networks. Machine learning techniques should be incorporated into systems for as
part of the disease prediction, diagnosis, or drug design. Individualized medicine is
gaining traction as a possible strategy to improve health. Patients must be treated.
We concentrate on individualized medicine here. on the basis of treatment
outcomes and trained, through personalized therapy.

Introduction
Each person, as well as his or her biology, is unique. The likelihood of developing
sickness and the extent to which a remedy affects a person differs from one person
to the next. Clinicians employ an amalgamation of genomic data, medical records,
lab tests, and other data on patients afflicted to help customise care in personalised
medicine.
Personalized medicine is defined as "a novel illness treatment and preventative
strategy that takes into account the individual variances in each person's genes,
surroundings, and lifestyle."
Medicine is essential for maintaining and extending life. Because not all body
systems are clinically identical, medicine must be tailored to the individual's body
system. Frequently, it has been noticed that one set of medicines works for one
category of patients while another category of patients with almost identical
clinical parameters cannot proceed from a mild or moderate disease to a severe
stage. Personalized medicine, with its more "customized" approach, may offer a
solution to this problem. Precision/individualized/customized medicine is another
name for it.

Machine Learning (ML) and Artificial Intelligence (AI) are frequently combined
(AI). However, machine learning (ML) is a field of artificial intelligence that finds
variable data patterns in order to predict or classify hidden or unknown patterns,
which may then be used for exploratory data analysis, data mining, and data
modelling. Based on clinical, genetic, laboratory, nutrition, and lifestyle-related
data, the ML algorithms suggest the possibility of finding target-based therapies.

AI IN HEALTHCARE
With the digitization of healthcare, advances such as AI can offer us assistance
analyze these endless sums of information to infer experiences and offer assistance
with choice making.

AI in healthcare is the utilization of complex calculations and software to imitate

human cognition within the investigation of complicated medical information
without coordinate human input. Since a seminal paper by Sir Alan Turing in 1950
AI has had numerous progresses in Natural Dialect Handling (NLP), Machine
Learning, Profound Learning, Discourse Acknowledgment, Virtual Agents , and
AI-optimized Equipment , among others.

Nowadays, AI is as of now utilized in healthcare for illustration to decrease false-

positive comes about in screening for breast cancer , ,reduce restorative translation
costs , progress physician workflow whereas diminishing and making a difference
to anticipate burnout , robotic surgery coming about in shorter length of
hospitalization and loss of blood and foreseeing mortality rates of patients with
acute heart disappointment .

Within the past, the foremost vital partner in healthcare, which is the persistent,
endured from a wide category of diseases which were treated with the same
medications, clearing out physicians to confuse over why they worked for a few
individuals and not others. Today researchers have started to get it, target, and
diagnose illnesses on a person level and AI can play a significant role in this
prepare given its interesting capabilities of detecting subtle illness particular
designs from a wide cluster of sources, such as atomic diagnostics, that people
would never recognize.

PERSONALIZED MEDICINE
With the utilize of machine learning applications, a subcategory of AI, that can
combine information from all state-of-the-art diagnostic tests and other assets,
there's more potential for personalized medicine than ever some time recently.
A high-level talk of two specific areas of medication will appear what AI, in
combination with all these unused advances, can and cannot do.

a) Lung Cancer
A 2018 narrative review on AI applications for non-small cell lung cancer
shows that there are already many applications being tested in this field.
Machine learning algorithms can be used to increase our understanding of
important genomic pathways in lung cancer, with the use of microarray data.
Also, machine learning can be used to predict which patient will respond to
newly developed checkpoint inhibitors or personalize radiation therapy, thereby
choosing an optimal treatment strategy. A key feature in the success of AI for
lung cancer is that many molecular abnormalities have already been discovered,
such as mutations in the epidermal growth factor receptor (EGFR) and
anaplastic lymphoma kinase (ALK) [33]. These very specific markers provide
an excellent starting point for algorithms to work from.
b) Sepsis
A similar narrative review of AI applications for sepsis was published in 2019,
showing that applications to improve diagnosis, treatment and prognosis exist
already. Many algorithms to predict sepsis onset have been developed, with
encouraging results, However, there are no clear molecular abnormalities
on which new algorithms can be trained. The rapid onset and heterogeneous
presentation of this syndrome makes it so, that the understanding of
pathophysiology remains poor when compared to that of lung cancer. The
potential of AI is therefore limited, as unique features needed to do adequate
predictions are not yet known. Machine learning has the ability to classify in the
absence of unique features, but to detect conditions like sepsis more data is
needed because of heterogenous presentation and unique features that are
needed in order to provide understanding to develop new treatments.
Algorithms can be trained to predict the best possible treatment on an individual
level, but can only consider the general treatments that exist today - antibiotics,
source control and intravenous fluids. Likely, better treatment options exist, but
the machine learning algorithms are limited by human knowledge
at this point in time. For AI to be able to provide personalized predictions for
treatment, meaningful data at scale is needed. Clinical trial data, molecular data
and general patient data needs to be integrated in advanced predictive models.
A broad understanding of pathophysiology in a certain field is needed in order
for AI to become valuable.
MAINSTREAMING AI IN HEALTHCARE
As talked about, a few infections particular challenges, such as with sepsis,
hold back the standard selection of AI in certain fields for presently, but
there are too a few common concerns and challenges almost the
appropriation of AI in healthcare which have to be tended to at a bigger
scale.
i) Challenges With AI
Challenges with the creation of AI in healthcare are centered
round explainability, liability, and privacy.
Furthermore, the scientific instructional device for healthcare
experts will should go through a rigorous transformation.
Lack of explainability of AI algorithms is probable to convey about
 a few resistances with the aid of using the scientific community. The more accurate the
algorithms, together with neural networks, the much less explainable they are. This "black
box" phenomenon makes it tough for
healthcare experts to get used to running with AI and
trusting the algorithm. In the end, physicians nevertheless should
make a very last choice and now no longer understand why you will make a
sure choice that will enhance many greater problems while an affected person is given the
incorrect diagnosis. Software builders should take under consideration and
prioritize expandability and accuracy.

Benefits of personalized medicine

1. It would reduce trial and error-based treatment decisions.

2. It would bring down the burdens associated with a condition both in terms
of health and finance.

3. Patient-centric medication through the integration of multi-modal data from

an individual.

4. More emphasis would be laid on preventive mode rather than the reactive
mode in medicine

5. Reduction in time, and cost associated with clinical trials conducted by

pharmaceuticals.

Role of Machine Learning

1. There is a scope of applying the algorithms of machine learning to the

genomic datasets which would enable the delivery of personalized medicines.

2. The use of multi-modal data helps in deeper analysis of large datasets which
improves the understanding of human health and disease by leaps and bound.
3. As ML is capable of identifying hidden patterns of data, many future
diseases can be prevented.

4. Advancement in the field of “in silico” experimental systems would improve

the efficiency of clinical trials which would reduce the time and cost associated
with clinical trials. The experimental system “in silico” refers to using computers
to run various experiments (Wanner, 2021).

5. Reduction of the burden on the healthcare system on screening of various

diseases of seriousness like lung cancer, covid19, heart diseases, etc.

Challenges for Machine Learning in the field of

Personalized Medicine

1. Optimization of application is required.

2. The knowledge base of the stakeholders which would involve physicians,

laboratory technicians, data analysts, programmers, and paramedical staff has
to be increased. Everyone needs to have a basic understanding of the
concerned domains.

Techniques of Machine Learning for Precision Medicine

There are three primary techniques for machine learning algorithms. These are
classification, regression, and clustering. Let’s have a look at the basic concept
of each of these.

1. Classification – Logistic Regression and Naive Bayes are the most common
supervised learning classification algorithms.
2. Regression – Linear Regression is the most common supervised learning
regression algorithm.

3. Clustering – K-means Algorithm, Mean Shift Algorithm, and Hierarchical

Clustering are the common algorithms. These are all unsupervised, i.e. target
variable is not available.

4. Classification and Regression combined – Support Vector Machine (SVM),

Decision Tree, Random Forest, and K-Nearest Neighbors are types of
supervised ML algorithms that are applicable in both classification and
regression predictive problems.

Another very important ML category is Reinforcement Learning which is

applied when a categorical target variable is available as well as when no target
variable is available. It has a got wide application in the area of auto-car and
optimized marketing. It is a semi-supervised algorithm.

Machine Learning and Precision Medicine in real world

The purpose of personalized medicine is to select and deliver patient-specific

treatments to achieve the best possible outcome. The challenge lies in
identifying an optimum treatment as the number of possible predictors of
good response like genetic and other biomarkers, and the option of treatments
is increasing.

In addition to this, as most clinical trials are based upon average treatment
effects, similar medicines become non-responsive for some patients and
responsive for some other patients.
An example in this regard is the primary analysis of the COMBINE Study which
is one of the largest clinical trials regarding treatments for alcohol dependence
in the USA. The study inferred that there was an impact of one of the
considered pharmacological treatments (naltrexone) but was non-responsive
for another, acamprosate (Tsai et al., 2016).

CART (Classification and Regression Trees) methods consider a large number

of potential predictors and identify combinations of patient characteristics and
good outcomes. Personalized medicine has a focus on whom a particular
treatment may be more effective than that of another. The application of a
modified tree-based approach indicates the possibility of selection of the best
individualized treatment based on baseline features (Tsai et al., 2016).
                                                                    Image Source: Tsai et al., 2016

The approach of modern-day medicine is based upon a population-wide

model which is intended to be applied to the overall population and is
optimized to have decent predictive performance on an average number of
people out of that population. This approach has done remarkably well for
decades but it ignores individual differences in treatment responses.

A better approach for capturing individual differences in treatment responses

is the patient-specific modeling approach. The personalized decision tree model
is a patient-specific modeling approach that performed a bit better than the
CART method (Adam, & Aliferis, 2019).

Gini impurity, information entropy, and variance reduction are 3 important

metrics for decision tree algorithm. Gini impurity is the more preferred metric
among the 3 metrics. It measures how a randomly chosen element is
incorrectly labeled.

Criteria for constructing a decision tree

1.  Every parent node of higher Gini impurity or information entropy is split
into child nodes to lower its Gini impurity or information entropy.
Gini impurity of pure sets = 0
2. The preferred split between the 2 child nodes would be the one in which
Gini impurity is higher would be split further.

3. Depending upon the complexity of parameters, the exploration of nodes is

discontinued.

Python libraries used in precision medicine

1. Scikit-learn –

One of the most important tools for ML. It is an open-source library that aids
in both supervised as well as unsupervised learning. From Scikit-learn various
estimators or predictors are imported to model a particular dataset. Scikit
provides us numerous models and ML algorithms. A few of them are

from sklearn.ensemble import RandomForestClassifier

from sklearn.linear_model import LogisticRegression
from sklearn.tree import DecisionTreeClassifier
from sklearn.model_selection import train_test_split
from sklearn.metrics import accuracy_score, confusion_matrix

2. pyGeno –

It is a Python package that pertains to precision medicine applications with a

special focus on genomics and proteomics. It is easy to use, has highly efficient
memory, and has a fast framework that allows users to easily explore subject-
specific genomes and proteomes. pyGeno has been developed by creating a
Python module that fully integrates within the Python environment making it
user-friendly. The users can make use of functionalities like SciPy, NumPy 11,
pandas, and matplotlib 13. It is available on https://pypi.python.org and can be
installed by writing a simple command “pip install pyGeno”.
Through get() function only, almost any query can be addressed and help()
function helps in retrieving integrated documents (Daouda, Perreault, &
Lemieuxb, 2016).  Its last version was released on 29th February 2020.

pip install pyGeno

from pyGeno.Genome import *

print(Exon.help())
Now, to build a personalized genome, we need to select the type of data we
are interested in from the BioMart database. After selecting a database, we
have to select a dataset that would be followed by filtration of the query.
Then, we need to select BioMart attributes, by default it would be “Ensembl
Gene ID” and “Ensembl Transcript ID”. Finally, the query will be displayed and
retrieved. The details have been illustrated in the image below

Importing the whole genome is an uphill task requiring 3 GB memory. In this

scenario, the bootstrap modules and data wrap are handy tools.
import pyGeno.bootstrap as B
B.printRemoteDatawraps()

A snapshot of the same has been provided below. It is to be noted that the file
type is GZ so it has to be extracted with “Archive extractor online” or any
other good extraction tools.

from pyGeno.Genome import *

g = Genome(name = "GRCh37.75")
prot = g.get(Protein, id = 'ENSP00000438917')[5]
print (prot.sequence)
print (prot.gene.biotype)

In the above lines, we are trying to extract protein sequence and gene biotype
which would act as a reference set and would be used to create a personalized
genome.
dummy = Genome(name = 'GRCh37.75', SNPs = 'dummySRY')
dummy = Genome(name = 'GRCh37.75', SNPs = 'dummySRY', SNPFilter =
myFilter())
dummy = Genome(name = 'GRCh37.75', SNPs = ['dummySRY', 'anotherSet'],
SNPFilter = myFilter())

Above are steps for creating a personalized genome. It allows clinicians to

work on the genomes and proteomes of patients. The entire working
mechanism of pyGeno in the field of precision medicine can be seen in the
image below.
CASE STUDIES

PRECISION MEDICINE IN CURRENT PANDEMIC

The present coronavirus disease (COVID-19) has emerged as a global pandemic, infecting
millions and killing thousands of patients. Even if there are many questions Findings regarding
pathophysiology remain unresolved COVID 19 Many aspects, including virus outbreaks,

Role, type and severity of ACE2 receptors Organ involvement, importance of coagulopathy,

Endothelial disease and the role of unbalanced cytokines answer. Clinicians are treating as the
pandemic spreads rapidly COVID 19 is in urgent need of effective treatment.
 The development of an effective vaccine is a long way off. probability. Well-designed
conducting in the face of a pandemic Clinical trials aimed at discovering effective treatments

Options also come with challenges chance.

A huge quantity of bad trials are a first-rate problem in important care remedy. This is essentially
because of the heterogeneous affected person population, with unique organic mechanisms and
unique organic responses to a disorder in man or woman sufferers. Rather than conducting trials the
usage of the traditional trial designs and bad affected person selection, precision-guided research
have a greater capacity to yield tremendous results. Precision remedy methods emphasize greater
specific diagnosis and remedy primarily based totally on more than a few biomarkers, which include
genetic editions, and statistics approximately sufferers’ environment, lifestyle, and behaviors. PM
methods can be beneficial in understanding versions in individuals’ susceptibility and responses to
COVID- 19. For instance, current research have determined that excessive COVID-19 infections are
related to gene editions on chromosome three (3p21.31) and chromosome 9 (9q34.2),1 ApoE e4
genotype,2 and loss-of-characteristic editions on X-chromosomal TLR7.three While there is debate
over the scientific importance of those editions, findings together with those may also offer
preliminary insights into why sufferers who seem comparable in phrases of demographics and
comorbidities can have massively unique responses.
In the ongoing pandemic, deciding upon the proper line of treatment for clinicians has become an
enormous challenge. The clinicians are confused about the efficacy of remdisivir and
corticosteroid on covid19 patients. ML algorithm can make a breakthrough in this area.

Lam et al. (2021) put forth that to evaluate the performance of corticosteroid versus remdesivir
on identifying patients with longer survival times, Gradient-boosted decision-tree models were
used. The models were trained and tested on data from 10 hospitals in the US on COVID-19 
adult patients (age ≥18 years). Significant findings in treated and nontreated patients were based
upon Fine and Gray proportional-hazards models.

The sample size was 2364 where 893 patients were treated with remdesivir, and 1471 were
treated with a corticosteroid. The confounding was adjusted and it was found that in the
populations identified by the algorithms, both corticosteroids and remdesivir were significantly
associated with an increase in survival time, with hazard ratios of 0.56 and 0.40, respectively
(both, P = 0.04). This contradicted the finding that neither corticosteroids nor remdesivir use
were associated with increased survival time (Lam et al., 2021). This indicates that the ML
algorithm holds promise in this field.

Though it's far too early to realize the entire effect of Personalized Medicine methods in addressing
COVID-19, we've got argued that “precision” is applicable to public fitness efforts in numerous ways,
which includes figuring out man or woman risks, assisting public fitness surveillance, and enhancing
vaccine efficacy. As Personalized Medicine methods are taken, we should recollect the feasible
unintended outcomes and make certain that interventions do now no longer exacerbate present
disparities. Precision methods are promising, however should complement, as opposed to replace,
efforts to bolster public fitness infrastructure and cope with essential reasons of illness.

Machine Learning-Based Method for Personalized and Cost-

Effective Detection of Alzheimer’s Disease

Diagnosis of Alzheimer’s disease(AD) is regularly difficult,

particularly early withinside the sickness procedure on the level of mild
cognitive impairment (MCI). Yet, it's miles at this level that treatment
is maximum possibly to be powerful, so there could be super blessings in
enhancing the analysis procedure. Using a machine
learning technique for personalised and cost-powerful analysis of
AD. It makes use of domestically weighted mastering to tailor a classifier
version to every affected person and computes the series of biomarkers
maximum informative or cost-powerful to diagnose sufferers. Using
ADNI information, we categorized AD as opposed to controls and MCI
sufferers who progressed to AD inside a year, towards individuals who
did not.

The technique carried out further to thinking about all information at

once, whilst significantly decreasing the number (and cost) of the
biomarkers needed to reap a assured analysis for every affected person.
Thus, it is able to contribute to a customized and powerful detection of
AD, and may show beneficial in scientific settings. Alzheimer’s disease
(AD) is the most common neurodegenerative
disease in older people [8]. There is a considerable delay
between the start of AD pathology and the clinical diagnosis of
AD dementia, which can only be confirmed by autopsy [8], [9].
Thus, it is very difficult to detect AD early and accurately [9],
and there is a need for intelligent means to support clinicians in
the personalized diagnosis of this disease [3].
To address such challenges, we test a proof-of-concept personalized
classifier for AD dementia and mild cognitive impairment
(MCI) patients based on biomarkers.
The Pool of known cases is a key part of the method. Interim
analyses (not shown due to space constraints) indicate that the
classification performance decreases when smaller subsamples
of the Pool are considered. Thus, it is essential to include a large
enough number of subjects in it. More extensive tests are needed
to determine how many cases should be included in the Pool. In
any case, in clinical practice, the Pool should be populated with local
data, which are more likely to reflect local life-style and
environmental factors that might affect the disease.
The results are promising and might be used to
support personalized diagnosis processes, while reducing the
number or cost of the biomarkers needed for diagnosis. Future
study is still needed but the framework presented in this letter
could be readily extended to other biomarkers and diseases.