August 2019 – Page 3 – The KGP Chronicle

Take it easy

People are often pushed for clinical tests that are expensive, time-consuming, uncomfortable and in plain sight even unnecessary. When it comes to life-threatening diseases such as cancer, where no one wants to take chances, there could be a higher risk of being mired in expensive, worrisome tests.

An ideal situation would be one where the advanced tests are recommended only for those who have a fair degree of certainty of carrying the disease. Even better if it can be assured that the preliminary screening for cancer is not only error free but also takes into account the patient’s preferences.

A team of researchers at IIT Kharagpur have done precisely that. They have devised an algorithm for detecting oesophageal cancer that accurately detects the probable cancer suspects. Not merely that, the algorithm also selects what combination of tests an individual patient should go through for this detection depending on the patient’s preference on costs and discomfort.

The outcome of the research was published in a recent Elsevier issue on ‘Artificial Intelligence in Medicine’. The research was conducted by Dr Asis Roy, Prof. Sourangshu Bhattacharya (Department of Computer Science and Engineering and Prof. Kalyan Guin (former faculty at the Vinod Gupta School of Management).

Customized or personalized medical services are becoming increasingly popular the world over in the prevention and treatment of diseases because it considers the patient’s individual genetics, clinical condition, environment and lifestyle in order to be the most effective. The researchers of IIT Kharagpur take this a notch above by proposing personalization of tests, and thus a personalized diagnosis system.

The methodology of customized clinical tests for oesophageal cancer was tested on the electronic medical records (EMRs) collected for more than 3,000 patients as part of a project carried out by a reputed hospital in Mumbai, India. The algorithm was found to yield an accuracy of 99.18% and sensitivity 100% using only demographic, lifestyle, patient history, and basic clinical tests. Among the patient details taken into account are weight, height, average income, lifestyle concerns like tobacco and alcohol consumption and medical history such as the incidence of cancer in the family.

EMR is often used by researchers to reveal hidden information through data mining. In fact, EMR has been used to detect heart disease, breast cancer and some diseases although not for oesophageal cancer. The researchers have delineated classifiers trained from EMR and the clinical tests in order to predict a new suspect [Among the 15 tests suggested by the medical practitioner for the screening are pressure, asthma, difficulty in swallowing, alteration of voice, Reflux Gastritis and Haematemesis. The tests suggested for each individual change with the inputs for comfort and costs.]

“The key idea is to design classifiers with near zero false normal rates, possibly at the cost of higher false abnormal,” says Prof Bhattacharya.

This means that there is a chance that cases detected to be positive for oesophageal cancer by the algorithm may turn out to be false after advanced tests, but there is no way that any patient who has oesophageal cancer will go undetected.

This method of screening can be adopted where a suspect is diagnosed initially by any health officer or clinician before approaching any doctor. The doctor can play his role once the system recommends a visit to a medical practitioner after analysing the captured data.

Dr Roy explains, “In third world countries like India, where a lot of the doctors’ time and precious resources are wasted, this model of treatment will reduce the waste since patients will not have to do all tests and will not have to go for unnecessary ones.” This will be particularly beneficial for rural areas, where hospitals are distant and there is acute shortage of doctors.

Besides, Dr Roy says, this model can be used for the detection of many other diseases by selecting appropriate features in EMR data and clinical tests. With minimized costs of healthcare, “more patients can afford to have the treatment either by bearing the cost on their own or by the insurance provider with an assumption that the premium will be low (the cost of overall treatment will be lower as compared to existing procedure).”

Additionally, says Dr Roy, healthcare providers can build a revolutionary new system for medical care by combining the data from diagnostic tests and medical history of patients to deliver enhanced value to patients. The research team expects health care service providers to implement this system as a soft sensor in preventing the disease by keeping the data in a cloud platform and alerting the person using mobile technology. “Undoubtedly the whole system can serve a large population by detecting a disease early with low cost and by giving satisfaction providing a freedom to choose the diagnostic tests,” says Dr Roy.

Combating the threat to humanity

“The biggest threat to human life comes from the smallest bugs,” reminded Prof. Anindya Sundar Ghosh, In-Charge of Molecular Microbiology Laboratory, Department of Biotechnology, IIT Kharagpur. He was recently at Birkbeck’s (University of London) Department of Biological Sciences to talk on “Penicillin interactive enzymes and tackling ß-lactam resistance in mycobacteria”. The occasion was provided by an international capacity-building workshop on the subject of antimicrobial resistance sponsored by the global challenges research fund (GCRF).

At Birkbeck University (Photo: Mr Harish Patel, Birkbeck School of Science)

Prof. Ghosh says, “The development of antimicrobial resistance is an evolutionary process and is inevitable as it involves the transfer of genes from one bacterium to another. Unless we increase our understanding of how infectious microbes keep evolving and develop resistance towards the antimicrobials used against them, we will never be able to protect ourselves from these life-threatening pathogens. But if we are able to spread awareness among the public and healthcare professionals, we will possibly be able to reduce the excessive use of antibiotics which will, in turn, prevent further aggravation of this problem that is already a serious threat to human existence.”

The Molecular Microbiology Laboratory (MMBL) of the Department of Biotechnology, IIT Kharagpur is involved in antimicrobial research with special emphasis on cell wall modulating penicillin-interactive enzymes including beta-lactamases in four different species of bacteria, namely, E. coli, Acenitobacter baumannii, Klebsiella pneumoniae and Mycobacterium smegmatis. At the workshop at Birkbeck, Prof. Ghosh highlighted his team’s research on Mycobacterium smegmatis.

Antibiotics of the beta-lactam group are extremely popular and hold the lion’s share in the antibiotic market. Due to their property of selective toxicity, beta-lactam antibiotics are extremely effective. These drugs target only the bacterial cell wall – peptidoglycan – and since this is not present in humans and animals, they do not harm the host. It is precisely because they are so effective, and hence popular, that there arises the threat of their misuse.

Prof. Ghosh says, “Mycobactrerial cell wall peptidoglycan (PG) is synthesized and remodelled by a set of transglycosylases and transpeptidases, though very little knowledge is available on their physiological actions. So far the known transglycosylases are PonA1 and PonA2 & transpeptidases are PBPA, PBPB, LdtA and LdtB. The unique feature of mycobacterial PG is that it is crosslinked upto 80% and it contains non-traditional 3–3 peptide crosslinks instead of traditional 4–3 crosslinks. However, very little is known about the remodelling of PG in mycobacteria.”

His team has discovered the physiology of two enzymes – MSMEG_2433 and MSMEG_2432 – possessing DD-carboxypeptidase activities that help in the peptidoglycan remodelling activities. The physiological role of these enzymes is established through various molecular genetics and biochemical studies, including mutational analysis. These two enzymes together help in the maintenance of 3-3 crosslinks in mycobacterial PG, the deletion of which converts the cross-link pattern from 3-3 to 4-3 and renders the cell wall leaky (Pandey et al, Journal of Bacteriology, 2018).

At the workshop Prof. Ghosh brought attention to the fact that MSMEG_2433 is a dual enzyme possessing both DD-carboxypeptidase and beta-lactamase activities (Bansal et al, Microbiology, 2015). These activities are influenced by a glutamic acid residue (G75) present in the omega-like loop of this enzyme, which in turn makes G75 a potential target for synthesis of inhibitory peptides that can be used in the future antimicrobial chemotherapy against mycobacterial infections.

A key area of research in MMBL is the discovery or synthesis of novel and efficient antibacterial drug molecules. In fact, a group of researchers in MMBL is exploring the antibacterial efficacy of various combinations of antibiotics and nano-particles. Birkbeck University features prominently in its scheme of things. Prof. Ghosh is already working in collaboration with Birkbeck’s faculty in designing inhibitors for beta-lactamases and other proteins that interact with penicillins and prevent their antibiotic action. At the workshop he set out several more opportunities for collaborative research, including finding molecules that prevent the formation of drug-resistant microbial biofilms.

Prof. Ghosh pointed out, “We need a worldwide drive against the menace of antimicrobial resistance. This may be through direct and indirect collaborative research that might subsequently help develop a combined front in antimicrobial research with sufficient funding from the international and national funding authorities.”

In this context it would be important to point out that IIT Kharagpur’s Department of Biotechnology organized an international conference entitled “International Conference on Contemporary Antimicrobial Research (ICCAR-2018)” in association with the Society for Antimicrobial Research (SAR). The conference focussed on the development of public awareness on antimicrobial resistance, networking of researchers around the globe, effective antibiotic effluent treatment, increased involvement of healthcare professionals and above all, the urgent requirement of sufficient funds for antimicrobial research.

Life Beyond Academics

It was a tad difficult to hunt for a vacant seat at the Netaji Auditorium on the Friday eve. The only empty ones were those reserved for the Deans, Professors and panelists in the first row. Even those were partially taken up by some guilt-laden students who couldn’t manage a place for themselves and had to encroach on space designated for the Faculty.

That there could be a flipside to an otherwise India’s premier academic Institute, was something newcomers were extremely curious about.

Professor Anandaroop Bhattacharya, Associate Dean, International Affairs, took up the microphone to welcome a packed hall of around 1200 students gathered to attend a panel session by IIT Kharagpur alumni on ‘Live and Learn – The KGP Way’. The panelists included 2002’s President Gold Medalist of IIT Kharagpur, Prof. Soumyajit Mandal, Assistant Professor, Case Western Reserve University, Cleveland, Ohio. And then there were the star performers in fields beyond academics and industry. There was the swimmer and athlete – Mr. Koushik Banerjee, from Nomura.Inc, Singapore, the Sitarist – Prof. Pallab Dasgupta, Dean Sponsored Research & Industrial Consultancy, IIT Kharagpur, the Violinist and Author – Mr Sudipto Das. And, of course, an amazing vocalist – Prof. Bhattacharya himself.

Professor Dasgupta, who was moderating the session, spoke for a couple of minutes giving a brief about how much effort, devotion and dedication it takes to maintain a good CGPA all throughout in order to bag a decent job, or pursue higher studies. He turned to Prof Soumyajit Mandal and asked, “Soumyajit, you are a President’s Gold Medal recipient. Did you ever bunk classes?” The expression on Prof. Mandal’s face clearly conveyed that he was not prepared for such a direct question. “So many of them… Don’t remember what time the first class started at…” was all he could say. “Professors knew that if there was one place where I had 100% attendance, it was the swimming pool,” added Mr Banerjee. The entire hall broke into a roll of laughter.

Perhaps the most dreaded part of hostel life in India is food. Hostelites across India complain that they might have received the best education but that came with a huge cost – hostel food. The two-minute noodle was their only mode of escape.

“What about mess food?” asked Prof. Dasgupta wryly, this time to Mr Banerjee. The panelists seemed to observe a one-minute silence at this question amidst the roar of claps and laughter from the audience. “There’s just one thing I can say,” said Prof. Dasgupta turning to the students, “Your future better halves will never complain about your eating habits, trust me.” “KGP mess food strengthens your digestive system to a different level altogether and you can survive on almost anything available under the sun.” added Mr. Banerjee. His words got drowned in a deafening roar of claps, whistles and laughter.

Turning to the audience, Prof Dasgupta asked, “How many of you have got bicycles here?” One hand from almost every seat went up in the air. “And how many of you wear slippers to class?” Amidst the rumbling sound of confusion, some smarty said aloud, “But our classes haven’t started yet…”. Prof. Dasgupta pointed out that Kgpians have devised a technology that connects bicycles to slippers. Slippers are used as bicycle-brakes– newcomers would soon realize that once they start their classes in full swing.” The students cracked up.

Amongst all the anecdotes, fun, laughter and sarcasm, the entire session centered around introducing IIT KGP from a new horizon altogether – a place that has much more to provide than just labs, lectures CGPAs and placement. There are things that the Institute, very subtly, drills into the psyche of its students. Humility, as Mr. Das pointed out, along with teamwork and leadership skills become second nature. “The best part of the Institute”, he continued, “is that it gives you an incredible support system in the form of classmates, roommates and hall-mates.” “Never fear failure, because there is space for everyone here,” quipped in Prof Soumyajit Mandal.

As the session drew to a close, Prof. Pallab Dasgupta pointed out that parents these days teach their children to compete more than to collaborate. He advised the students to stay away from this league

Now that was a googly. For students who had competed nationally, often with each other, even for that one mark, it would take some time for the message to sink in. But perhaps it had already started to sink in. When students left the hall, they were laughing and jostling with each other, almost with the carefree abandon you see among children who have just started school.

Book Release at the Event:

‘The Broken Amoretti’, a book authored by Mr Sudipto Das was released by Prof Pallab Dasgupta on this occasion.